Caracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR)

Pseudomonas aeruginosa es un microorganismo que presenta resistencia en los entornos clínicos. Son diferentes los mecanismos por los cuales logra evadir los antimicrobianos, uno de ellos son los sistemas de dos componentes. PhoQ y PhoP son un sistema de dos componentes conocido principalmente en Sal...

Full description

Autores:
Rodríguez Vásquez, Laura Ximena
Tipo de recurso:
Trabajo de grado de pregrado
Fecha de publicación:
2021
Institución:
Colegio Mayor de Cundinamarca
Repositorio:
Repositorio Colegio Mayor de Cundinamarca
Idioma:
spa
OAI Identifier:
oai:repositorio.unicolmayor.edu.co:unicolmayor/5553
Acceso en línea:
https://repositorio.unicolmayor.edu.co/handle/unicolmayor/5553
Palabra clave:
Sensibilidad
MDR
Pseudomonas aeruginosa
Sistema de dos componentes
PhoQ
Rights
closedAccess
License
Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2021
id UCOLMAYOR2_165a1d0ba84c70fad2f3fe2a23d1b23c
oai_identifier_str oai:repositorio.unicolmayor.edu.co:unicolmayor/5553
network_acronym_str UCOLMAYOR2
network_name_str Repositorio Colegio Mayor de Cundinamarca
repository_id_str
dc.title.spa.fl_str_mv Caracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR)
title Caracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR)
spellingShingle Caracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR)
Sensibilidad
MDR
Pseudomonas aeruginosa
Sistema de dos componentes
PhoQ
title_short Caracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR)
title_full Caracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR)
title_fullStr Caracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR)
title_full_unstemmed Caracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR)
title_sort Caracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR)
dc.creator.fl_str_mv Rodríguez Vásquez, Laura Ximena
dc.contributor.advisor.none.fl_str_mv Sánchez Mora, Ruth Mélida
Romero Calderón, Ibeth Cristina
dc.contributor.author.none.fl_str_mv Rodríguez Vásquez, Laura Ximena
dc.subject.lemb.none.fl_str_mv Sensibilidad
MDR
topic Sensibilidad
MDR
Pseudomonas aeruginosa
Sistema de dos componentes
PhoQ
dc.subject.proposal.spa.fl_str_mv Pseudomonas aeruginosa
Sistema de dos componentes
PhoQ
description Pseudomonas aeruginosa es un microorganismo que presenta resistencia en los entornos clínicos. Son diferentes los mecanismos por los cuales logra evadir los antimicrobianos, uno de ellos son los sistemas de dos componentes. PhoQ y PhoP son un sistema de dos componentes conocido principalmente en Salmonella sp., es por esto que su caracterización in silico en Pseudomonas aeruginosa aporta al conocimiento sobre la identificación de nuevos marcadores moleculares asociados a virulencia y resistencia. En el presente proyecto se caracterizaron los genes PhoQ-PhoP de dos cepas MDR de P. aeruginosa haciendo uso de herramientas bioinformáticas con el objetivo de buscar mutaciones frente a las cepas sensibles a medicamentos, realizar un análisis filogenético con ortólogos y determinar características de las proteínas codificadas por estos genes. Se logró observar una mutación de cambio de sentido en PhoQ con un cambio de tirosina por fenilalanina, un distanciamiento filogenético de P. aeruginosa en comparación a ortólogos de estos genes por las diferencias funcionales y ambientales de las distintas especies y se obtuvo modelos tridimensionales de buena calidad lo cual permite realizar la búsqueda de compuestos que tengan afinidad de unión con estas proteínas, paso principal en el diseño racional de nuevos medicamentos. Estos resultados pueden ser usados a futuro para el desarrollo de posibles blancos terapéuticos o para la inhibición selectiva de P. aeruginosa en alternativas terapéuticas.
publishDate 2021
dc.date.issued.none.fl_str_mv 2021-09-03
dc.date.accessioned.none.fl_str_mv 2022-05-11T01:44:09Z
dc.date.available.none.fl_str_mv 2022-05-11T01:44:09Z
dc.type.spa.fl_str_mv Trabajo de grado - Pregrado
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_7a1f
dc.type.coarversion.spa.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.content.spa.fl_str_mv Text
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/bachelorThesis
dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/TP
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_7a1f
status_str publishedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unicolmayor.edu.co/handle/unicolmayor/5553
url https://repositorio.unicolmayor.edu.co/handle/unicolmayor/5553
dc.language.iso.spa.fl_str_mv spa
language spa
dc.relation.references.spa.fl_str_mv Yagui M. Resistencia antimicrobiana: nuevo enfoque y oportunidad. Rev. perú. med. exp. 2018; 35: 1726-4634. Disponible en: http://www.scielo.org.pe/scielo.php?script=sci_arttext&pid=S1726-463420180001000 02
Quiñones D. Resistencia antimicrobiana: evolución y perspectivas actuales ante el enfoque "Una salud". Rev Cubana Med Trop. 2017; 69 (3): 1561-3054. Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0375-07602017000300009
Ponce S, Arredondo R, López Y. La resistencia a los antibióticos: Un grave problema global. Gac Med Mex. 2015;151:681-9. Disponible en: https://www.medigraphic.com/pdfs/gaceta/gm-2015/gm155r.pdf
Ruiz P., & Cantón R. Epidemiology of antibiotic resistance in Pseudomonas aeruginosa. Implications for empiric and definitive therapy. Rev Esp Quimioter. (2017). 30 (Suppl. 1): 8-12. Disponible en: https://seq.es/seq/0214-3429/30/suppl1/01ruiz.pdf
Tierney A & Rather P. Roles of two-component regulatory systems in antibiotic resistance. Future Microbiol. 2019; 14(6): 533–552. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526388/
Yang B, Liu C, Pan X, Fu W, Fan Z, Jin Y, et al. Identification of Novel phoP-phoQ Regulated Genes that Contribute to Polymyxin B Tolerance in Pseudomonas aeruginosa. Microorganisms. 2021; 9(2): 344. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916210/
Bou G. Relación entre resistencia y virulencia en bacterias de interés clínico. Enferm Infecc Microbiol Clin. 2014; 32(1):1–3. Disponible en: https://www.elsevier.es/es-revista-enfermedades-infecciosas-microbiologia-clinica-28- pdf-S0213005X13003352
OMS. Carga mundial de infecciones asociadas a la atención sanitaria [Internet]. Disponible en: https://www.who.int/gpsc/country_work/burden_hcai/es/ [Consultado el 15 de enero de 2020]
Barchiesi J, Castelli M, Venanzio G, Colombo M, García E. The PhoP/PhoQ System and Its Role in Serratia marcescens Pathogenesis. J Bacteriol. 2012; 194(11): 2949–2961. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370626/
Instituto Nacional de Salud. Infecciones asociadas a dispositivos [Internet]. Disponible en: https://www.ins.gov.co/buscador-eventos/Lineamientos/Pro_Infecciones%20asociada s%20a%20dispositivos.pdf#search=IAAS [Consultado el 15 de enero de 2020]
Boyd S, Vasudevan A, Moore L, Brewer C, Gilchrist M, Costelloe C, et al. Validating a prediction tool to determine the risk of nosocomial multidrug-resistant Gram-negative bacilli infection in critically ill patients: A retrospective case–control study. J Glob Antimicrob Resist. 2020; 22: 826-831. Disponible en: https://www.sciencedirect.com/science/article/pii/S2213716520301855?via%3Dihub
Angelettia S, Cella E, Prosperi M, Spoto S, Fogolari M, Florio L, et al. Multi-drug resistant Pseudomonas aeruginosa nosocomial strains: Molecular epidemiology and evolution. Microb. Pathog. 2018; 123: 233-241. Disponible en: https://www.sciencedirect.com/science/article/abs/pii/S0882401018306557?via%3Dih ub
Tummler B. Emerging therapies against infections with Pseudomonas aeruginosa. F1000 Faculty Rev. 2019; 8: 1371. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688719/
Garbajosa P, Cantón R. Epidemiology of antibiotic resistance in Pseudomonas aeruginosa. Implications for empiric and definitive therapy. Rev Esp Quimioter. 2017; 30: 8-12. Disponible en: https://seq.es/seq/0214-3429/30/suppl1/01ruiz.pdf
Wieland K, Chhatwal P, Vonberg R. Nosocomial outbreaks caused by Acinetobacter baumannii and Pseudomonas aeruginosa: Results of a systematic review. Am. J. Infect. Control. 2018; 46: 643-648. Disponible en: https://pubmed.ncbi.nlm.nih.gov/29398072/
INS. Infecciones asociadas a dispositivos en UCI. [Internet]. Disponible en: https://www.ins.gov.co/buscador-eventos/Informesdeevento/INFECCIONES%20ASO CIADAS%20A%20DISPOSITIVOS%20PE%20II%202021.pdf#search=pseudomonas %20infecciones
Morales J, Andrade J. Risk factors associated with mortality and antibiotic susceptibility patterns in Pseudomonas aeruginosa bacteremia. Bol. Med. Hosp. Infant. 2006; 63 (5): 1665-1146. Disponible en: http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1665-114620060005000 02#:~:text=La%20mortalidad%20asociada%20a%20bacteriemias,incidencia%20de% 20infecciones%20por%20P.
Valderrama S, González PF, Caro MA, Ardila N, Ariza B, Gil F, et al. Factores de riesgo para bacteriemia por Pseudomonas aeruginosa resistente a carbapenémicos adquirida en un hospital colombiano. Biomédica. 2016; 36 (1): 69-77. Disponible en: https://revistabiomedica.org/index.php/biomedica/article/view/2784
Saavedra A, Duarte C, Nilse M, Realpe M. Caracterización de aislamientos de Pseudomonas aeruginosa productores de carbapenemasas de siete departamentos de Colombia. Biomédica 2014; 34 (1):217-23. Disponible en: https://revistabiomedica.org/index.php/biomedica/article/view/1685
Hérnandez A, Yague G, Vázquez E, Simon M, Moreno L, Canteras M. Infecciones nosocomiales por Pseudomonas aeruginosa multiresistente incluido carbapenémicos: factores predictivos y pronósticos. Estudio prospectivo 2016-2017. Rev Esp Quimioter. 2018 Apr; 31(2): 123–130. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159385/
Derakhshanab S, Hosseinzadehc A. Resistant Pseudomonas aeruginosa carrying virulence genes in hospitalized patients with urinary tract infection from Sanandaj, west of Iran. Gene rep. 2020; 20: 100675. Disponible en: https://doi.org/10.1016/j.genrep.2020.100675
Horcajada J, Montero M, Oliver A, Sorlí L, Luque S, Gómez S, et al. Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections. Clin Microbiol Rev. 2019; 32(4): e00031-19. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6730496/
Recio R, Mancheño M, Viedma E, Villa J, Orellana M, Lora J, et al. Predictors of Mortality in Bloodstream Infections Caused by Pseudomonas aeruginosa and Impact of Antimicrobial Resistance and Bacterial Virulence. Antimicrob Agents Chemother. 2020; 64(2): e01759-19. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985728/
Sharma A, Sangwan N, Negi V, Kohli P, Khurana J, Lakshmi D, et al. Pan-genome dynamics of Pseudomonas gene complements enriched across hexachlorocyclohexane dumpsite. BMC Genomics. 2015; 16(1): 313. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405911/
Orellana M, Pachecho N, Costa J, Mendez K, Miossec M, Meneses C. In-Depth Genomic and Phenotypic Characterization of the Antarctic Psychrotolerant Strain Pseudomonas sp. MPC6 Reveals Unique Metabolic Features, Plasticity, and Biotechnological Potential. Front Microbiol. 2019; 10: 1154. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543543/
Lee C, Klockgether J, Fischer S, Trcek J, Tummler B, Romling R. Why? – Successful Pseudomonas aeruginosa clones with a focus on clone C. FEMS Microbiol Rev. 2020 Nov; 44(6): 740–762. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685784/
Parkins M, Somayaji R, Waters V. Epidemiology, Biology, and Impact of Clonal Pseudomonas aeruginosa Infections in Cystic Fibrosis. Clin Microbiol Rev. 2018; 31(4): e00019-1. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148191/
Schwartz D, Cantor C. Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis. Cell. 1984;37(1): 67-75. Disponible en: https://pubmed.ncbi.nlm.nih.gov/6373014/
Jolley K, Bray J, Maiden M. Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res. 2018; 3: 124. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192448
Yan Y, Yao X, Li H, Zhou Z, Huang W, Stratton C, et al. A Novel Pseudomonas aeruginosa Strain with an oprD Mutation in Relation to a Nosocomial Respiratory Infection Outbreak in an Intensive Care Unit. J Clin Microbiol. 2014; 52(12): 4388–4390. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313324/
Xu Y, Zheng X, Zeng W, Chen T, Liao W, Lin J, et al. Mechanisms of Heteroresistance and Resistance to Imipenem in Pseudomonas aeruginosa. Infect Drug Resist. 2020; 13: 1419–1428. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234976/
Yoon E, Kim D, Lee H, Sun H, Hwan J, Soo Y, et al. Mortality dynamics of Pseudomonas aeruginosa bloodstream infections and the influence of defective OprD on mortality: prospective observational study. J Antimicrob Chemother. 2019; 74(9): 2774-2783. Disponible en: https://pubmed.ncbi.nlm.nih.gov/31236593/
Balasubramanian D, Kumari H, Mathee K. Pseudomonas aeruginosa AmpR: an acute–chronic switch regulator. Pathog Dis. 2015 Mar; 73(2): 1–14. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542883/
Khatua B, Van J, Pronab B, Chaudhry R, Mandal C. Sialylation of Outer Membrane Porin Protein D: A Mechanistic Basis of Antibiotic Uptake in Pseudomonas aeruginosa. Mol Cell Proteomics. 2014; 13(6): 1412–1428. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047463/
Tsutsumi Y, Tomita H, Tanimoto K. Identification of Novel Genes Responsible for Overexpression of ampC in Pseudomonas aeruginosa PAO1. Antimicrob Agents Chemother. 2013; 57(12): 5987–5993. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837884/
Ho-Fung C, Krahn T, Gilmour C, Mullen E, Poole K. AmgRS-mediated envelope stress-inducible expression of the mexXY multidrug efflux operon of Pseudomonas aeruginosa. Microbiologyopen. 2015 Feb; 4(1): 121–135. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335980
Puja H, Bolard A, Nogués A, Plésiat, Jeannot K. The Efflux Pump MexXY/OprM Contributes to the Tolerance and Acquired Resistance of Pseudomonas aeruginosa to Colistin. Antimicrob Agents Chemother. 2020 Apr; 64(4): e02033-19. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179290/
Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. Substrate Specificities of MexAB-OprM, MexCD-OprJ, and MexXY-OprM Efflux Pumps in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2000 Dec; 44(12): 3322–3327. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC90200/
Poole K, Ho-Fung C, Gilmour C, Hao Y, Lam J. Polymyxin Susceptibility in Pseudomonas aeruginosa Linked to the MexXY-OprM Multidrug Efflux System. Antimicrob Agents Chemother. 2015 Dec; 59(12): 7276–7289. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649153/
Nouri R, Ahangarzadeh M, Hasani A, Aghazadeh M, Asgharzadeh M. The role of gyrA and parC mutations in fluoroquinolones-resistant Pseudomonas aeruginosa isolates from Iran. Braz J Microbiol. 2016; 47(4): 925–930. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052375/
Feng X, Zhang Z, Li X, Song Y, Kang J, Yin D, et al. Mutations in gyrB play an important role in ciprofloxacin-resistant Pseudomonas aeruginosa. Infect Drug Resist. 2019; 12: 261–272. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371945/
Bruchmann S, Dötsch A, Nouri B, Chaberny I, Häussler S. Quantitative Contributions of Target Alteration and Decreased Drug Accumulation to Pseudomonas aeruginosa Fluoroquinolone Resistance. Antimicrob Agents Chemother. 2013 Mar; 57(3): 1361–1368. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591863/
Colombia. Resolución Nº 008430 de 1993 por la cual se establecen las normas científicas, técnicas y administrativas para la investigación en salud. (Boletín oficial del Estado, 4 de octubre de 1993).
Vélez E. Bacilos Gram negativos no fermentadores de glucosa. En: Orjuela O, Gallejo CR. Bacteriología Aplicada. Manual de Procedimientos. Colombia: Kimpres; 2014. p 101-102.
Burguillos L. Resistencia antibiótica en Pseudomonas aeruginosa: Situación epidemiológica en España y alternativas de tratamiento. [Pregrado]. Universidad Complutense; 2018. Disponible en: http://147.96.70.122/Web/TFG/TFG/Memoria/LAURA%20BRAVO-BURGUILLOS%20 ROS.pdf
Paz V, Mangwani S, Martínez A, Álvarez D, Solano S, Vázquez R. Pseudomonas aeruginosa: patogenicidad y resistencia antimicrobiana en la infección urinaria. Rev. chil. infectol. 2019; 36 (2): 0716-1018. Disponible en: https://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0716-1018201900020018 0
Ruíz L. Pseudomonas aeruginosa: aportación al conocimiento de su estructura y al de los mecanismos que contribuyen a su resistencia a los antimicrobianos. [Doctoral].Universidad de Barcelona; 2017. Disponible en: https://www.tdx.cat/bitstream/handle/10803/2521/LRM_TESIS.pdf
Ghadam P, Akhlaghi F, Abdi A. One-step purification and characterization of alginate lyase from a clinical Pseudomonas aeruginosa with destructive activity on bacterial biofilm. Iran J Basic Med Sci. 2017; 20(5): 467–473. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478773/
Moradali M, Ghods S, Rehm B. Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence. Front Cell Infect Microbiol. 2017; 7: 39. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310132/
Bedard E, Prevost M, Deziel E. Pseudomonas aeruginosa in premise plumbing of large buildings. Microbiologyopen. 2016; 5(6): 937–956. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221438/
Conceição J, Pereira P, Damasceno F, Ribeiro C, Oliveira S, Tranches A. Ozone against Pseudomonas aeruginosa biofilms in contact lenses storage cases. Rev Inst Med Trop Sao Paulo. 2019; 61: e23. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481249/
Pachori P, Gothalwal R, Gandhi P. Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit; a critical review. Genes Dis. 2019; 6(2): 109–119. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545445/
Liu T, Zhang Y, Wan Q. Pseudomonas aeruginosa bacteremia among liver transplant recipients. Infect Drug Resist. 2018; 11: 2345–2356. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247952/
Tran M, Wibowo D, Rehm B. Pseudomonas aeruginosa Biofilms. Int J Mol Sci. 2020; 21(22): 8671. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698413/
Malhotra S, Hayes D, Wozniak D. Cystic Fibrosis and Pseudomonas aeruginosa: the Host-Microbe Interface. Clin Microbiol Rev. 2019; 32(3): e00138-18. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589863/
Mui T, Kretzschmar M, Bertrand X, Bootsma M. Tracking Pseudomonas aeruginosa transmissions due to environmental contamination after discharge in ICUs using mathematical models. PLoS Comput Biol. 2019; 15(8): e1006697. Disponible en: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006697
Bachta K, Allen J, Cheung B, Chiu C, Hauser A. Systemic Infection Facilitates Transmission of Pseudomonas aeruginosa. BioRxi. 2019. Disponible en: https://www.biorxiv.org/content/10.1101/765339v1.full
Mensa J, Barberán J, Soriano A, Llinares P, Marco F, Cantón R, et al. Antibiotic selection in the treatment of acute invasive infections by Pseudomonas aeruginosa: Guidelines by the Spanish Society of Chemotherapy. Rev Esp Quimioter. 2018; 31(1): 78–100. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159363/
Raman G, Avendano E, Chan J, Merchant S, Puzniak L. Risk factors for hospitalized patients with resistant or multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis. Antimicrob Resist Infect Control. 2018; 7: 79. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032536/
Behzadi P, Barath Z, Gajdacs M. It’s Not Easy Being Green: A Narrative Review on the Microbiology, Virulence and Therapeutic Prospects of Multidrug-Resistant Pseudomonas aeruginosa. Antibiotics (Basel). 2021; 10(1): 42. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823828/
Carmine A, Gomes A, Melo F, Ardisson D, Castagna A, Lunkes V. Characterization of a bacteriophage with broad host range against strains of Pseudomonas aeruginosa isolated from domestic animal. BMC Microbiol. 2019; 19: 134. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580649/
Pfalzgraff A, Brandenburg K, Weindl G. Antimicrobial Peptides and Their Therapeutic Potential for Bacterial Skin Infections and Wounds. Front Pharmacol. 2018; 9: 281. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882822/
Ruffin M, Brochiero E. Repair Process Impairment by Pseudomonas aeruginosa in Epithelial Tissues: Major Features and Potential Therapeutic Avenues. Front Cell Infect Microbiol. 2019; 9: 182. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554286/
Elmouaden C, Laglaoui A, Ennanei L, Bakkali M, Abid M. Virulence genes and antibiotic resistance of Pseudomonas aeruginosa isolated from patients in the Northwestern of Morocco. J. Infect. Dev. Ctries. 2019; 13(10):892-898. Disponible en: https://jidc.org/index.php/journal/article/view/32084019
Pejčića M, Stojanović-Radića Z, Genčić M, Dimitrijevića M, Radulovićb N. Anti-virulence potential of basil and sage essential oils: Inhibition of biofilm formation, motility and pyocyanin production of Pseudomonas aeruginosa isolates. Food Chem. Toxicol. 2020; 141:111431. Disponible en: https://doi.org/10.1016/j.fct.2020.111431
Sawa T, Shimizu M, Moriyama K, Wiener J. Association between Pseudomonas aeruginosa type III secretion, antibiotic resistance, and clinical outcome: a review. Crit Care. 2014; 18(6): 668. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331484
Wang C, Liu X, Wang J, Zhou J, Cui Z, Hui L. Design and characterization of a polyamine derivative inhibiting the expression of type III secretion system in Pseudomonas aeruginosa. Sci Rep. 2016; 6: 30949. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971474/
Ullah W, Qasim M, Rahman H, Jie Y, Muhammad N. Beta-lactamase-producing Pseudomonas aeruginosa: Phenotypic characteristics and molecular identification of virulence genes. Chin Med J. 2017; 80 (3): 173-177. Disponible en: https://doi.org/10.1016/j.jcma.2016.08.011
Schinner S, Engelhardt F, Preusse M, Gesine J, Tomasch J, Haussler S. Genetic determinants of Pseudomonas aeruginosa fitness during biofilm growth. Biofilm. 2020; 2: 100023. Disponible en: https://doi.org/10.1016/j.bioflm.2020.100023
Francis V, Stevenson E, Porter S. Two-component systems required for virulence in Pseudomonas aeruginosa. FEMS Microbiol Lett. 2017; 364(11): fnx104. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812489/
Groisman E. The Pleiotropic Two-Component Regulatory System PhoP-PhoQ. mBio. 2001; 1835-1842. Disponible en: https://jb.asm.org/content/183/6/1835
Samantha A, Vrielink A. Lipid A Phosphoethanolamine Transferase: Regulation, Structure and Immune Response. J. Mol. Biol. 2020; 432 (18): 5184-5196. Disponible en: https://www.sciencedirect.com/science/article/pii/S002228362030320X
Raheem M, Xue M, Ahmad H, Ahmad M, Tipu M, Afzal G, et al. Adaptation to host specific bacterial pathogens drive rapid evolution of novel PhoP/PhoQ regulation pathway modulating the virulence. Microb. Pathog. 2020; 141: 103997. Disponible en: https://doi.org/10.1016/j.micpath.2020.103997
Cao L, Wang J, Sun L, Kong Z, Wu Q, Wang Z, et al. Transcriptional analysis reveals the relativity of acid tolerance and antimicrobial peptide resistance of Salmonella. Microb. Pathog. 2019; 136: 103701. Disponible en: https://doi.org/10.1016/j.micpath.2019.103701
Tsai M, Liang Y, Chen C, Chiu C. Characterization of Salmonella resistance to bile during biofilm formation. J Microbiol Immunol Infect. 2020; 53 (4): 518-524. Disponible en: https://doi.org/10.1016/j.jmii.2019.06.003
Gunn J, Richards S. Recognition and Integration of Multiple Environmental Signals by the Bacterial Sensor Kinase PhoQ. Cell Host Microbe. 2007; 1 (3): 163-165. Disponible en: https://www.cell.com/fulltext/S1931-3128(07)00075-3
Prost L, Daley M, Sage V, Bader M, Moual H, Klevit R, et al. Activation of the Bacterial Sensor Kinase PhoQ by Acidic pH. Mol. cell. 2007; 26 (2): 165-174. Disponible en: https://www.sciencedirect.com/science/article/pii/S1097276507001530#:~:text=Suma ry,transcriptional%20program%20essential%20for%20virulence.&text=PhoQ%2 also%20binds%20and%20is,sensor%20domain%20to%20pH%205.5
Carabajal M, Asquith C, Laitinen T, Tizzard G, Yim L, Rial A, et al. Quinazoline Based Antivirulence Compounds Selectively Target Salmonella PhoP/PhoQ Signal Transduction System. mBio. 2020; 64 (1): e01744-19. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187569/
Liu L, Zheng S. Transcriptional regulation of Yersinia pestis biofilm formation. Microb. Pathog. 2019; 131: 212-217. Disponible en: https://doi.org/10.1016/j.micpath.2019.04.011
Erickson D, Russel C, Johnson K, Hileman T, Steward R. PhoP and OxyR transcriptional regulators contribute to Yersinia pestis virulence and survival within Galleria mellonella. Microb. Pathog. 2011; 51 (6): 389-395. Disponible en: https://doi.org/10.1016/j.micpath.2011.08.008
Bozue J, Mou S, Moody K, Cote C, Trevino S, Fritz D, Worsham P. The role of the phoPQ operon in the pathogenesis of the fully virulent CO92 strain of Yersinia pestis and the IP32953 strain of Yersinia pseudotuberculosis. Microb. Pathog. 2011; 50 (6): 314-321. Disponible en: https://doi.org/10.1016/j.micpath.2011.02.005
Lin Z, Cai X, Chen M, Ye L, Wu Y, Wang X, et al. Virulence and Stress Responses of Shigella flexneri Regulated by PhoP/PhoQ. Front. Microbiol. 2018; 8:2689. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775216/
Nakka S, Qi M, Zhao Y. The Erwinia amylovora PhoPQ system is involved in resistance to antimicrobial peptide and suppresses gene expression of two novel type III secretion systems. Microbiol. Res. 2010; 165 (8): 665-673. Disponible en: https://www.sciencedirect.com/science/article/pii/S0944501309001165?via%3Dihub
Serra M. La resistencia microbiana en el contexto actual y la importancia del conocimiento y aplicación en la política antimicrobiana. Rev haban cienc méd. 2017; 16 (3): 1729-519. Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1729519X20170003 00011
ISGLOBAL. Los 4 frentes de batalla contra la resistencia a los antibióticos. [Internet]. Disponible en: https://www.isglobal.org/informe-la-batalla-contra-las-resistencias [Consultado el 30 de enero de 2020]
Pintilie L, Stefaniu A. In Silico Drug Design and Molecular Docking Studies of Some Quinolone Compound. Molecular Docking and Molecular Dynamics. 2019. Disponible en: https://www.intechopen.com/books/molecular-docking-and-molecular-dynamics/-em-i n-silico-em-drug-design-and-molecular-docking-studies-of-some-quinolone-compoun d
Jeukens J, Freschi J, Kukavica‐Ibrulj I, Emond J, Tucker N & Levesque R. Genomics of antibiotic‐resistance prediction in Pseudomonas aeruginosa. Ann N Y Acad Sci. 2019; 1435(1): 5–17. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379567/
Soukarieh F, Vico E, Dubern J, Gomes J, Halliday N, Crespo M, et al. In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa. Molecules. 2018; 23(2): 257. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017655/
Solanki V, Tiwari M & Tiwari V. Prioritization of potential vaccine targets using comparative proteomics and designing of the chimeric multi-epitope vaccine against Pseudomonas aeruginosa. Sci Rep. 2019; 9: 5240. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437148/
National Center for Biotechnology Information (NCBI). Basic Local Alignment Search Tool (BLAST). Disponible en: https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastn&PAGE_TYPE=B lastSearch&BLAST_SPEC=&LINK_LOC=blasttab&LAS T_PAGE=blastp
MEGA. Disponible en: https://www.megasoftware.net/
Khan S. Árboles filogenéticos. [Internet]. Khan Academy. 2016. [citado 20 de mayo del 2021]. Disponible en: https://es.khanacademy.org/science/high-schoolbiology/hs-evolution/hs-phylogeny/a/ phylogenetic-trees
Martínez-Lage, A y González-Tizón, A. Aplicaciones de la bioinformática en la elaboración de filogenias moleculares. 2004. Fundación Alfredo Brañas. 53-81. Disponible en: https://www.udc.es/grupos/gibe/uploads/gibe/andres%20ana/filogenias.pdf
Nei M & Kumar S. Molecular Evolution and Phylogenetics. 1 ed. New York: Oxford University Press: 2000.
Protparam tool. Disponible en: https://web.expasy.org/protparam/
PROSITE Database of protein domains, families and functional sites. Disponible en: https://prosite.expasy.org/
SWISS-MODEL. Disponible en: https://swissmodel.expasy.org/
PSIPRED. Disponible en: http://bioinf.cs.ucl.ac.uk/psipred/
GOR IV. Disponible en: https://npsaprabi.ibcp.fr/cgibin/npsa_automat.pl?page=/NPSA/npsa_gor4.html
Protein Structure Analisis Web. Disponible en: https://prosa.services.came.sbg.ac.at/prosa.php
Jochumsen N, Marvig R, Damkkiaer S, Lyngkli p R, Paulander W, Molin S, et al. The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is shaped by strong epistatic interactions. Nat. Commun. 2016; 7: 13002. Disponible en: https://www.nature.com/articles/ncomms13002
Barrow K, Know D. Alterations in Two-Component Regulatory Systems of phoPQ and pmrAB Are Associated with Polymyxin B Resistance in Clinical Isolates of Pseudomonas aeruginosa. J. Clin. Microbiol. 2020; 53 (12). Disponible en: https://journals.asm.org/doi/10.1128/AAC.00893-09
Meng L, Liu H, Lan T, Dong L, Hu H, Zhao S, et al. Antibiotic Resistance Patterns of Pseudomonas spp. Isolated From Raw Milk Revealed by Whole Genome Sequencing. Front. Microbiol. 2020; 11:1005. Disponible en: https://www.frontiersin.org/articles/10.3389/fmicb.2020.01005/full
Gutu A, Sgambati N, Strasbourger P, Brannon M, Jacobs M, Haugen E, et al. Polymyxin Resistance of Pseudomonas aeruginosa phoQ Mutants Is Dependent on Additional Two-Component Regulatory Systems. J. Clin. Microbiol. 2013; 57 (5). Disponible en: https://journals.asm.org/doi/10.1128/aac.02353-12?permanently=true
Gooderham J, Hancock R. Regulation of virulence and antibiotic resistance by two-component regulatory systems in Pseudomonas aeruginosa. FEMS Microbiology Reviews. 2009; 33 (2): 279-294. Disponible en: https://academic.oup.com/femsre/article/33/2/279/588178
Olaitan A, Morand S, Rolain J. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front. Microbiol. 2014; 5:643.Disponible en: https://www.frontiersin.org/articles/10.3389/fmicb.2014.00643/full
Miller A, Brannon M, Stevens L, Krogh H, Selgrade S, Miller S, et al. PhoQ Mutations Promote Lipid A Modification and Polymyxin Resistance of Pseudomonas aeruginosa Found in Colistin-Treated Cystic Fibrosis Patients. Antimicrob Agents Chemother. 2011; 55(12): 5761–5769. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232818/
Molina L, Udaondo Z, Duque E, Fernández M, Molina M, Roca A, et al. Antibiotic Resistance Determinants in a Pseudomonas putida Strain Isolated from a Hospital. PloS one. 2014. Disponible en: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081604
Macfarlane E, Kwasnicka A, Ochs M, Hancock R. PhoP–PhoQ homologues in Pseudomonas aeruginosa regulate expression of the outer-membrane protein OprH and polymyxin B resistance. Mol. Microbiol. 2002; 34 (2): 305-316. Disponible en: https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2958.1999.01600.
Francis V, Stevenson E, Porter S. Two-component systems required for virulence in Pseudomonas aeruginosa. FEMS Microbiol Lett. 2017; 364(11): fnx104. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812489/
McPhee K, Lewenza S, Hanckock R. Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa. Mol. Microbiol. 2003; 50 (1): 205-217. Disponible en: https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2958.2003.03673.x
McPhee J, Bains M, Winsor G, Lewenza S, Brazas M, Brinkman F, et al. Contribution of the PhoP-PhoQ and PmrA-PmrB Two-Component Regulatory Systems to Mg2+-Induced Gene Regulation in Pseudomonas aeruginosa. J Bacteriol. 2006; 188(11): 3995–4006. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1482896/
Olaitan A, Morand S, Rolain J. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front. Microbiol. 2014; 5:643. Disponible en: https://www.frontiersin.org/articles/10.3389/fmicb.2014.00643/full
Prost L, Daley M, Bader M, Klevit Miller S. The PhoQ Histidine Kinases of Salmonella and Pseudomonas spp. are Structurally and Functionally Different: Evidence that pH and Antimicrobial Peptide Sensing Contribute to Mammalian Pathogenesis. Mol Microbiol. 2008; 69(2): 503–519. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2555970/
Gunn J. The Salmonella PmrAB regulon: lipopolysaccharide modifications, antimicrobial peptide resistance and more. Trends Microbiol. 2008; 16 (6): 284-290. Disponible en: https://sci-hub.se/https://doi.org/10.1016/j.tim.2008.03.007
Gellatly S. Regulation of the PhoQ-PhoP two-component system in Pseudomonas aeruginosa and its role in virulence. [Doctoral]. University of Victoria; 2012.
Brinkman F, MacFarlane E, Warrener P, Hancock R. Evolutionary Relationships among Virulence-Associated Histidine Kinases. Infect Immun. 2001; 69(8): 5207–5211. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC98623/
Molnar K, Bonomi M, Pellarin R, Clinthorne G, Gonzalez G, Goldberg S, et al. Cys-scanning Disulfide crosslinking and Bayesian modeling probe the transmembrane signaling mechanism of the histidine kinase, PhoQ. Structure. 2014; 22(9): 1239–1251. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322757
Lesley J, Waldburger C. Comparison of the Pseudomonas aeruginosa andEscherichia coli PhoQ Sensor Domains. J. Biol. Chem. 2001; 276 (33): P30827- 30833. Disponible en: https://www.jbc.org/article/S0021-9258(20)80227-/fulltext#fig1
Matamouros S, Hager K, Miller S. HAMP Domain Rotation and Tilting Movements Associated with Signal Transduction in the PhoQ Sensor Kinase. mBio. 2015; 6(3): e00616. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447245/
Stock A, Robinson V, Goudreau P. Two-Component Signal Transduction. Biochemistry. 2000; 69:183-215. Disponible en: https://www.annualreviews.org/doi/10.1146/annurev.biochem.69.1.183
Velikova N, Fulle S, Manso A, Mechkarska M, Finn P, Conlon J, et al. Putative histidine kinase inhibitors with antibacterial effect against multi-drug resistant clinical isolates identified by in vitro and in silico screens. Sci Rep. 2016; 6: 26085. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865847/
Viarengo G. Identificación y caracterización de compuestos antibacterianos a partir de productos naturales o semisintéticos. [Doctoral]. Universidad Nacional del Litoral; 2015.
Cheung J, Hendrickson W. Sensor Domains of Two-Component Regulatory Systems. Curr Opin Microbiol. 2010; 13(2): 116–123. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078554/
Ahmad A, Fadel F, Kreuzer C, Ba M, Pélissier G, Bornet O, et al. Structural and functional insights into the periplasmic detector domain of the GacS histidine kinase controlling biofilm formation in Pseudomonas aeruginosa. Sci Rep. 2017; 7: 11262. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595915/
dc.rights.spa.fl_str_mv Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2021
dc.rights.uri.spa.fl_str_mv https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/closedAccess
dc.rights.creativecommons.spa.fl_str_mv Atribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)
dc.rights.coar.spa.fl_str_mv http://purl.org/coar/access_right/c_14cb
rights_invalid_str_mv Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2021
https://creativecommons.org/licenses/by-nc-sa/4.0/
Atribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)
http://purl.org/coar/access_right/c_14cb
eu_rights_str_mv closedAccess
dc.format.extent.spa.fl_str_mv 68p.
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Universidad Colegio Mayor de Cundinamarca
dc.publisher.faculty.spa.fl_str_mv Facultad de Ciencias de la Salud
dc.publisher.place.spa.fl_str_mv Bogotá
dc.publisher.program.spa.fl_str_mv Bacteriología y Laboratorio Clínico
institution Colegio Mayor de Cundinamarca
bitstream.url.fl_str_mv https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/8/FORMATO%20CARTA%20DERECHOS%20DE%20AUTOR%20FIRMA%20DECANA%20IIP2021%20Rodriguez.docx.pdf.txt
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/10/Sustentaci%c3%b3n%20proyecto%20de%20grado%202021%20Rodriguez%20Vasquez.pptx.txt
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/11/Caracterizaci%c3%b3n%20in%20silico%20de%20los%20genes%20de%20virulencia%20PhoP%20-PhoQ%20en%20cepas%20de%20Pseudomonas%20aeruginosa%20fenotipo%20multidrogo-resistente%20%28MDR%29.docx.pdf.txt
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/13/PORTADA%20TRABAJOS%20DE%20GRADO%20IIP%202021-LAURA%20RODRIGUEZ.docx.pdf.txt
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/15/FORMATO%20DERECHOS%20DE%20AUTOR%20TG%202021%20-LAURA%20RODRIGUEZ.doc.pdf.txt
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/17/CARTA%20DECANO%20DERECHOS%20DE%20AUTOR%20MODALIDADES%20DE%20GRADO%20IIP%202021.pdf.txt
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/9/FORMATO%20CARTA%20DERECHOS%20DE%20AUTOR%20FIRMA%20DECANA%20IIP2021%20Rodriguez.docx.pdf.jpg
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/12/Caracterizaci%c3%b3n%20in%20silico%20de%20los%20genes%20de%20virulencia%20PhoP%20-PhoQ%20en%20cepas%20de%20Pseudomonas%20aeruginosa%20fenotipo%20multidrogo-resistente%20%28MDR%29.docx.pdf.jpg
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/14/PORTADA%20TRABAJOS%20DE%20GRADO%20IIP%202021-LAURA%20RODRIGUEZ.docx.pdf.jpg
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/16/FORMATO%20DERECHOS%20DE%20AUTOR%20TG%202021%20-LAURA%20RODRIGUEZ.doc.pdf.jpg
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/18/CARTA%20DECANO%20DERECHOS%20DE%20AUTOR%20MODALIDADES%20DE%20GRADO%20IIP%202021.pdf.jpg
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/7/license.txt
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/19/Caracterizaci%c3%b3n%20in%20silico%20de%20los%20genes%20de%20virulencia%20PhoP%20-PhoQ%20en%20cepas%20de%20Pseudomonas%20aeruginosa%20fenotipo%20multidrogo-resistente%20%28MDR%29.docx.pdf
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/20/Sustentaci%c3%b3n%20proyecto%20de%20grado%202021%20Rodriguez%20Vasquez.pptx
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/21/FORMATO%20CARTA%20DERECHOS%20DE%20AUTOR%20FIRMA%20DECANA%20IIP2021%20Rodriguez.docx.pdf
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/22/FORMATO%20DERECHOS%20DE%20AUTOR%20TG%202021%20-LAURA%20RODRIGUEZ.doc.pdf
bitstream.checksum.fl_str_mv 0dc9aed7f7ae83ef28db96afadb50d6e
de31de11e15f13cf870f4411ba3ea702
9c6b6f5db10c3b4d2c5ee8fea17f0885
356279c86b9467d9140927296db29da2
4b113bdf9ec14ff1a1c6d5b4d6ee5b4a
15c691b6fdeaef1bc6d123286851a1f8
13d0e8df2bfb95a17ed466f5220a9c26
ef7d0ffff8f88966cb243bc85cb695de
0e501bac6d0157891856cd06ae4ed127
adf149ec9a903f76dc0085b754de0599
a0b679346419d6b2cfdc9d604a17cf4a
2f9959eaf5b71fae44bbf9ec84150c7a
9095ef5a6c544b9579854364017f5daf
3372e9dac5ca2adb0fc8976766d7dfdf
f52385d980521fc923b51bef80471042
1a32bc978374f030af469b27747ffb21
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Biblioteca Digital Unicolmayor
repository.mail.fl_str_mv repositorio@unicolmayor.edu.co
_version_ 1812210086866583552
spelling Sánchez Mora, Ruth Mélidaefe8f5fbfdf7ec7c24ba850634bfbb9aRomero Calderón, Ibeth Cristina1be6cd68f2562dc4b43f161eb1ab77a0Rodríguez Vásquez, Laura Ximena3233d17ed4c4dabb597e8d5cf95f7c642022-05-11T01:44:09Z2022-05-11T01:44:09Z2021-09-03https://repositorio.unicolmayor.edu.co/handle/unicolmayor/5553Pseudomonas aeruginosa es un microorganismo que presenta resistencia en los entornos clínicos. Son diferentes los mecanismos por los cuales logra evadir los antimicrobianos, uno de ellos son los sistemas de dos componentes. PhoQ y PhoP son un sistema de dos componentes conocido principalmente en Salmonella sp., es por esto que su caracterización in silico en Pseudomonas aeruginosa aporta al conocimiento sobre la identificación de nuevos marcadores moleculares asociados a virulencia y resistencia. En el presente proyecto se caracterizaron los genes PhoQ-PhoP de dos cepas MDR de P. aeruginosa haciendo uso de herramientas bioinformáticas con el objetivo de buscar mutaciones frente a las cepas sensibles a medicamentos, realizar un análisis filogenético con ortólogos y determinar características de las proteínas codificadas por estos genes. Se logró observar una mutación de cambio de sentido en PhoQ con un cambio de tirosina por fenilalanina, un distanciamiento filogenético de P. aeruginosa en comparación a ortólogos de estos genes por las diferencias funcionales y ambientales de las distintas especies y se obtuvo modelos tridimensionales de buena calidad lo cual permite realizar la búsqueda de compuestos que tengan afinidad de unión con estas proteínas, paso principal en el diseño racional de nuevos medicamentos. Estos resultados pueden ser usados a futuro para el desarrollo de posibles blancos terapéuticos o para la inhibición selectiva de P. aeruginosa en alternativas terapéuticas.Pseudomonas aeruginosa is a microorganism that has resistance in clinical settings. The mechanisms by which it manages to evade antimicrobials are different, one of them being the two-component systems. PhoQ and PhoP are a two-component system known mainly in Salmonella sp., Which is why their in silico characterization in Pseudomonas aeruginosa contributes to the knowledge on the identification of new molecular markers associated with virulence and resistance. In this project, the PhoQ-PhoP genes of two MDR strains of P. aeruginosa were characterized using bioinformatics tools in order to search for mutations against drug-sensitive strains, perform a phylogenetic analysis with orthologs and determine protein characteristics. encoded by these genes. It was possible to observe a missense mutation in PhoQ with a change from phenylalanine to tyrosine, a phylogenetic distancing of P. aeruginosa in comparison to orthologs of these genes due to the functional and environmental differences of the different species and three-dimensional models of good quality which allows the search for compounds that have binding affinity with these proteins, a main step in the rational design of new drugs. These results can be used in the future for the development of possible therapeutic targets or for the selective inhibition of P. aeruginosa in therapeutic alternativesResumen 9 Introducción 11 1. Objetivos 13 1.1 Objetivo general 13 1.2 Objetivos específicos 13 2. Antecedentes 14 3. Bases legales 16 4. Marco teórico 17 4.1 Características generales de Pseudomonas aeruginosa 17 4.2 Enfermedades o infecciones ocasionadas por Pseudomonas aeruginosa 17 4.2.1 Modo de transmisión 18 4.2.2 Tratamiento y resistencia en P. aeruginosa 18 4.2.3 Alternativas terapéuticas 19 4.3 Patogenicidad y virulencia de Pseudomonas aeruginosa 20 4.3.1 Genes de virulencia y resistencia en Pseudomonas aeruginosa 21 4.4 Función biológica de PhoP y PhoQ en microorganismos 21 4.5 Importancia de los estudios in silico en resistencia bacteriana 24 5. Metodología 25 6. Resultados 29 7. Discusión 47 8. Conclusiones 51 Referencias bibliográficas 51PregradoBacteriólogo(a) y Laboratorista Clínico68p.application/pdfspaUniversidad Colegio Mayor de CundinamarcaFacultad de Ciencias de la SaludBogotáBacteriología y Laboratorio ClínicoDerechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2021https://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/closedAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_14cbCaracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR)Trabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1fhttp://purl.org/coar/version/c_970fb48d4fbd8a85Textinfo:eu-repo/semantics/bachelorThesishttps://purl.org/redcol/resource_type/TPinfo:eu-repo/semantics/publishedVersionYagui M. Resistencia antimicrobiana: nuevo enfoque y oportunidad. Rev. perú. med. exp. 2018; 35: 1726-4634. Disponible en: http://www.scielo.org.pe/scielo.php?script=sci_arttext&pid=S1726-463420180001000 02Quiñones D. Resistencia antimicrobiana: evolución y perspectivas actuales ante el enfoque "Una salud". Rev Cubana Med Trop. 2017; 69 (3): 1561-3054. Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0375-07602017000300009Ponce S, Arredondo R, López Y. La resistencia a los antibióticos: Un grave problema global. Gac Med Mex. 2015;151:681-9. Disponible en: https://www.medigraphic.com/pdfs/gaceta/gm-2015/gm155r.pdfRuiz P., & Cantón R. Epidemiology of antibiotic resistance in Pseudomonas aeruginosa. Implications for empiric and definitive therapy. Rev Esp Quimioter. (2017). 30 (Suppl. 1): 8-12. Disponible en: https://seq.es/seq/0214-3429/30/suppl1/01ruiz.pdfTierney A & Rather P. Roles of two-component regulatory systems in antibiotic resistance. Future Microbiol. 2019; 14(6): 533–552. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526388/Yang B, Liu C, Pan X, Fu W, Fan Z, Jin Y, et al. Identification of Novel phoP-phoQ Regulated Genes that Contribute to Polymyxin B Tolerance in Pseudomonas aeruginosa. Microorganisms. 2021; 9(2): 344. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916210/Bou G. Relación entre resistencia y virulencia en bacterias de interés clínico. Enferm Infecc Microbiol Clin. 2014; 32(1):1–3. Disponible en: https://www.elsevier.es/es-revista-enfermedades-infecciosas-microbiologia-clinica-28- pdf-S0213005X13003352OMS. Carga mundial de infecciones asociadas a la atención sanitaria [Internet]. Disponible en: https://www.who.int/gpsc/country_work/burden_hcai/es/ [Consultado el 15 de enero de 2020]Barchiesi J, Castelli M, Venanzio G, Colombo M, García E. The PhoP/PhoQ System and Its Role in Serratia marcescens Pathogenesis. J Bacteriol. 2012; 194(11): 2949–2961. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370626/Instituto Nacional de Salud. Infecciones asociadas a dispositivos [Internet]. Disponible en: https://www.ins.gov.co/buscador-eventos/Lineamientos/Pro_Infecciones%20asociada s%20a%20dispositivos.pdf#search=IAAS [Consultado el 15 de enero de 2020]Boyd S, Vasudevan A, Moore L, Brewer C, Gilchrist M, Costelloe C, et al. Validating a prediction tool to determine the risk of nosocomial multidrug-resistant Gram-negative bacilli infection in critically ill patients: A retrospective case–control study. J Glob Antimicrob Resist. 2020; 22: 826-831. Disponible en: https://www.sciencedirect.com/science/article/pii/S2213716520301855?via%3DihubAngelettia S, Cella E, Prosperi M, Spoto S, Fogolari M, Florio L, et al. Multi-drug resistant Pseudomonas aeruginosa nosocomial strains: Molecular epidemiology and evolution. Microb. Pathog. 2018; 123: 233-241. Disponible en: https://www.sciencedirect.com/science/article/abs/pii/S0882401018306557?via%3Dih ubTummler B. Emerging therapies against infections with Pseudomonas aeruginosa. F1000 Faculty Rev. 2019; 8: 1371. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688719/Garbajosa P, Cantón R. Epidemiology of antibiotic resistance in Pseudomonas aeruginosa. Implications for empiric and definitive therapy. Rev Esp Quimioter. 2017; 30: 8-12. Disponible en: https://seq.es/seq/0214-3429/30/suppl1/01ruiz.pdfWieland K, Chhatwal P, Vonberg R. Nosocomial outbreaks caused by Acinetobacter baumannii and Pseudomonas aeruginosa: Results of a systematic review. Am. J. Infect. Control. 2018; 46: 643-648. Disponible en: https://pubmed.ncbi.nlm.nih.gov/29398072/INS. Infecciones asociadas a dispositivos en UCI. [Internet]. Disponible en: https://www.ins.gov.co/buscador-eventos/Informesdeevento/INFECCIONES%20ASO CIADAS%20A%20DISPOSITIVOS%20PE%20II%202021.pdf#search=pseudomonas %20infeccionesMorales J, Andrade J. Risk factors associated with mortality and antibiotic susceptibility patterns in Pseudomonas aeruginosa bacteremia. Bol. Med. Hosp. Infant. 2006; 63 (5): 1665-1146. Disponible en: http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1665-114620060005000 02#:~:text=La%20mortalidad%20asociada%20a%20bacteriemias,incidencia%20de% 20infecciones%20por%20P.Valderrama S, González PF, Caro MA, Ardila N, Ariza B, Gil F, et al. Factores de riesgo para bacteriemia por Pseudomonas aeruginosa resistente a carbapenémicos adquirida en un hospital colombiano. Biomédica. 2016; 36 (1): 69-77. Disponible en: https://revistabiomedica.org/index.php/biomedica/article/view/2784Saavedra A, Duarte C, Nilse M, Realpe M. Caracterización de aislamientos de Pseudomonas aeruginosa productores de carbapenemasas de siete departamentos de Colombia. Biomédica 2014; 34 (1):217-23. Disponible en: https://revistabiomedica.org/index.php/biomedica/article/view/1685Hérnandez A, Yague G, Vázquez E, Simon M, Moreno L, Canteras M. Infecciones nosocomiales por Pseudomonas aeruginosa multiresistente incluido carbapenémicos: factores predictivos y pronósticos. Estudio prospectivo 2016-2017. Rev Esp Quimioter. 2018 Apr; 31(2): 123–130. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159385/Derakhshanab S, Hosseinzadehc A. Resistant Pseudomonas aeruginosa carrying virulence genes in hospitalized patients with urinary tract infection from Sanandaj, west of Iran. Gene rep. 2020; 20: 100675. Disponible en: https://doi.org/10.1016/j.genrep.2020.100675Horcajada J, Montero M, Oliver A, Sorlí L, Luque S, Gómez S, et al. Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections. Clin Microbiol Rev. 2019; 32(4): e00031-19. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6730496/Recio R, Mancheño M, Viedma E, Villa J, Orellana M, Lora J, et al. Predictors of Mortality in Bloodstream Infections Caused by Pseudomonas aeruginosa and Impact of Antimicrobial Resistance and Bacterial Virulence. Antimicrob Agents Chemother. 2020; 64(2): e01759-19. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985728/Sharma A, Sangwan N, Negi V, Kohli P, Khurana J, Lakshmi D, et al. Pan-genome dynamics of Pseudomonas gene complements enriched across hexachlorocyclohexane dumpsite. BMC Genomics. 2015; 16(1): 313. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405911/Orellana M, Pachecho N, Costa J, Mendez K, Miossec M, Meneses C. In-Depth Genomic and Phenotypic Characterization of the Antarctic Psychrotolerant Strain Pseudomonas sp. MPC6 Reveals Unique Metabolic Features, Plasticity, and Biotechnological Potential. Front Microbiol. 2019; 10: 1154. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543543/Lee C, Klockgether J, Fischer S, Trcek J, Tummler B, Romling R. Why? – Successful Pseudomonas aeruginosa clones with a focus on clone C. FEMS Microbiol Rev. 2020 Nov; 44(6): 740–762. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685784/Parkins M, Somayaji R, Waters V. Epidemiology, Biology, and Impact of Clonal Pseudomonas aeruginosa Infections in Cystic Fibrosis. Clin Microbiol Rev. 2018; 31(4): e00019-1. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148191/Schwartz D, Cantor C. Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis. Cell. 1984;37(1): 67-75. Disponible en: https://pubmed.ncbi.nlm.nih.gov/6373014/Jolley K, Bray J, Maiden M. Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res. 2018; 3: 124. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192448Yan Y, Yao X, Li H, Zhou Z, Huang W, Stratton C, et al. A Novel Pseudomonas aeruginosa Strain with an oprD Mutation in Relation to a Nosocomial Respiratory Infection Outbreak in an Intensive Care Unit. J Clin Microbiol. 2014; 52(12): 4388–4390. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313324/Xu Y, Zheng X, Zeng W, Chen T, Liao W, Lin J, et al. Mechanisms of Heteroresistance and Resistance to Imipenem in Pseudomonas aeruginosa. Infect Drug Resist. 2020; 13: 1419–1428. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234976/Yoon E, Kim D, Lee H, Sun H, Hwan J, Soo Y, et al. Mortality dynamics of Pseudomonas aeruginosa bloodstream infections and the influence of defective OprD on mortality: prospective observational study. J Antimicrob Chemother. 2019; 74(9): 2774-2783. Disponible en: https://pubmed.ncbi.nlm.nih.gov/31236593/Balasubramanian D, Kumari H, Mathee K. Pseudomonas aeruginosa AmpR: an acute–chronic switch regulator. Pathog Dis. 2015 Mar; 73(2): 1–14. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542883/Khatua B, Van J, Pronab B, Chaudhry R, Mandal C. Sialylation of Outer Membrane Porin Protein D: A Mechanistic Basis of Antibiotic Uptake in Pseudomonas aeruginosa. Mol Cell Proteomics. 2014; 13(6): 1412–1428. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047463/Tsutsumi Y, Tomita H, Tanimoto K. Identification of Novel Genes Responsible for Overexpression of ampC in Pseudomonas aeruginosa PAO1. Antimicrob Agents Chemother. 2013; 57(12): 5987–5993. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837884/Ho-Fung C, Krahn T, Gilmour C, Mullen E, Poole K. AmgRS-mediated envelope stress-inducible expression of the mexXY multidrug efflux operon of Pseudomonas aeruginosa. Microbiologyopen. 2015 Feb; 4(1): 121–135. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335980Puja H, Bolard A, Nogués A, Plésiat, Jeannot K. The Efflux Pump MexXY/OprM Contributes to the Tolerance and Acquired Resistance of Pseudomonas aeruginosa to Colistin. Antimicrob Agents Chemother. 2020 Apr; 64(4): e02033-19. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179290/Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. Substrate Specificities of MexAB-OprM, MexCD-OprJ, and MexXY-OprM Efflux Pumps in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2000 Dec; 44(12): 3322–3327. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC90200/Poole K, Ho-Fung C, Gilmour C, Hao Y, Lam J. Polymyxin Susceptibility in Pseudomonas aeruginosa Linked to the MexXY-OprM Multidrug Efflux System. Antimicrob Agents Chemother. 2015 Dec; 59(12): 7276–7289. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649153/Nouri R, Ahangarzadeh M, Hasani A, Aghazadeh M, Asgharzadeh M. The role of gyrA and parC mutations in fluoroquinolones-resistant Pseudomonas aeruginosa isolates from Iran. Braz J Microbiol. 2016; 47(4): 925–930. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052375/Feng X, Zhang Z, Li X, Song Y, Kang J, Yin D, et al. Mutations in gyrB play an important role in ciprofloxacin-resistant Pseudomonas aeruginosa. Infect Drug Resist. 2019; 12: 261–272. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371945/Bruchmann S, Dötsch A, Nouri B, Chaberny I, Häussler S. Quantitative Contributions of Target Alteration and Decreased Drug Accumulation to Pseudomonas aeruginosa Fluoroquinolone Resistance. Antimicrob Agents Chemother. 2013 Mar; 57(3): 1361–1368. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591863/Colombia. Resolución Nº 008430 de 1993 por la cual se establecen las normas científicas, técnicas y administrativas para la investigación en salud. (Boletín oficial del Estado, 4 de octubre de 1993).Vélez E. Bacilos Gram negativos no fermentadores de glucosa. En: Orjuela O, Gallejo CR. Bacteriología Aplicada. Manual de Procedimientos. Colombia: Kimpres; 2014. p 101-102.Burguillos L. Resistencia antibiótica en Pseudomonas aeruginosa: Situación epidemiológica en España y alternativas de tratamiento. [Pregrado]. Universidad Complutense; 2018. Disponible en: http://147.96.70.122/Web/TFG/TFG/Memoria/LAURA%20BRAVO-BURGUILLOS%20 ROS.pdfPaz V, Mangwani S, Martínez A, Álvarez D, Solano S, Vázquez R. Pseudomonas aeruginosa: patogenicidad y resistencia antimicrobiana en la infección urinaria. Rev. chil. infectol. 2019; 36 (2): 0716-1018. Disponible en: https://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0716-1018201900020018 0Ruíz L. Pseudomonas aeruginosa: aportación al conocimiento de su estructura y al de los mecanismos que contribuyen a su resistencia a los antimicrobianos. [Doctoral].Universidad de Barcelona; 2017. Disponible en: https://www.tdx.cat/bitstream/handle/10803/2521/LRM_TESIS.pdfGhadam P, Akhlaghi F, Abdi A. One-step purification and characterization of alginate lyase from a clinical Pseudomonas aeruginosa with destructive activity on bacterial biofilm. Iran J Basic Med Sci. 2017; 20(5): 467–473. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478773/Moradali M, Ghods S, Rehm B. Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence. Front Cell Infect Microbiol. 2017; 7: 39. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310132/Bedard E, Prevost M, Deziel E. Pseudomonas aeruginosa in premise plumbing of large buildings. Microbiologyopen. 2016; 5(6): 937–956. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221438/Conceição J, Pereira P, Damasceno F, Ribeiro C, Oliveira S, Tranches A. Ozone against Pseudomonas aeruginosa biofilms in contact lenses storage cases. Rev Inst Med Trop Sao Paulo. 2019; 61: e23. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481249/Pachori P, Gothalwal R, Gandhi P. Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit; a critical review. Genes Dis. 2019; 6(2): 109–119. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545445/Liu T, Zhang Y, Wan Q. Pseudomonas aeruginosa bacteremia among liver transplant recipients. Infect Drug Resist. 2018; 11: 2345–2356. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247952/Tran M, Wibowo D, Rehm B. Pseudomonas aeruginosa Biofilms. Int J Mol Sci. 2020; 21(22): 8671. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698413/Malhotra S, Hayes D, Wozniak D. Cystic Fibrosis and Pseudomonas aeruginosa: the Host-Microbe Interface. Clin Microbiol Rev. 2019; 32(3): e00138-18. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589863/Mui T, Kretzschmar M, Bertrand X, Bootsma M. Tracking Pseudomonas aeruginosa transmissions due to environmental contamination after discharge in ICUs using mathematical models. PLoS Comput Biol. 2019; 15(8): e1006697. Disponible en: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006697Bachta K, Allen J, Cheung B, Chiu C, Hauser A. Systemic Infection Facilitates Transmission of Pseudomonas aeruginosa. BioRxi. 2019. Disponible en: https://www.biorxiv.org/content/10.1101/765339v1.fullMensa J, Barberán J, Soriano A, Llinares P, Marco F, Cantón R, et al. Antibiotic selection in the treatment of acute invasive infections by Pseudomonas aeruginosa: Guidelines by the Spanish Society of Chemotherapy. Rev Esp Quimioter. 2018; 31(1): 78–100. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159363/Raman G, Avendano E, Chan J, Merchant S, Puzniak L. Risk factors for hospitalized patients with resistant or multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis. Antimicrob Resist Infect Control. 2018; 7: 79. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032536/Behzadi P, Barath Z, Gajdacs M. It’s Not Easy Being Green: A Narrative Review on the Microbiology, Virulence and Therapeutic Prospects of Multidrug-Resistant Pseudomonas aeruginosa. Antibiotics (Basel). 2021; 10(1): 42. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823828/Carmine A, Gomes A, Melo F, Ardisson D, Castagna A, Lunkes V. Characterization of a bacteriophage with broad host range against strains of Pseudomonas aeruginosa isolated from domestic animal. BMC Microbiol. 2019; 19: 134. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580649/Pfalzgraff A, Brandenburg K, Weindl G. Antimicrobial Peptides and Their Therapeutic Potential for Bacterial Skin Infections and Wounds. Front Pharmacol. 2018; 9: 281. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882822/Ruffin M, Brochiero E. Repair Process Impairment by Pseudomonas aeruginosa in Epithelial Tissues: Major Features and Potential Therapeutic Avenues. Front Cell Infect Microbiol. 2019; 9: 182. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554286/Elmouaden C, Laglaoui A, Ennanei L, Bakkali M, Abid M. Virulence genes and antibiotic resistance of Pseudomonas aeruginosa isolated from patients in the Northwestern of Morocco. J. Infect. Dev. Ctries. 2019; 13(10):892-898. Disponible en: https://jidc.org/index.php/journal/article/view/32084019Pejčića M, Stojanović-Radića Z, Genčić M, Dimitrijevića M, Radulovićb N. Anti-virulence potential of basil and sage essential oils: Inhibition of biofilm formation, motility and pyocyanin production of Pseudomonas aeruginosa isolates. Food Chem. Toxicol. 2020; 141:111431. Disponible en: https://doi.org/10.1016/j.fct.2020.111431Sawa T, Shimizu M, Moriyama K, Wiener J. Association between Pseudomonas aeruginosa type III secretion, antibiotic resistance, and clinical outcome: a review. Crit Care. 2014; 18(6): 668. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331484Wang C, Liu X, Wang J, Zhou J, Cui Z, Hui L. Design and characterization of a polyamine derivative inhibiting the expression of type III secretion system in Pseudomonas aeruginosa. Sci Rep. 2016; 6: 30949. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971474/Ullah W, Qasim M, Rahman H, Jie Y, Muhammad N. Beta-lactamase-producing Pseudomonas aeruginosa: Phenotypic characteristics and molecular identification of virulence genes. Chin Med J. 2017; 80 (3): 173-177. Disponible en: https://doi.org/10.1016/j.jcma.2016.08.011Schinner S, Engelhardt F, Preusse M, Gesine J, Tomasch J, Haussler S. Genetic determinants of Pseudomonas aeruginosa fitness during biofilm growth. Biofilm. 2020; 2: 100023. Disponible en: https://doi.org/10.1016/j.bioflm.2020.100023Francis V, Stevenson E, Porter S. Two-component systems required for virulence in Pseudomonas aeruginosa. FEMS Microbiol Lett. 2017; 364(11): fnx104. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812489/Groisman E. The Pleiotropic Two-Component Regulatory System PhoP-PhoQ. mBio. 2001; 1835-1842. Disponible en: https://jb.asm.org/content/183/6/1835Samantha A, Vrielink A. Lipid A Phosphoethanolamine Transferase: Regulation, Structure and Immune Response. J. Mol. Biol. 2020; 432 (18): 5184-5196. Disponible en: https://www.sciencedirect.com/science/article/pii/S002228362030320XRaheem M, Xue M, Ahmad H, Ahmad M, Tipu M, Afzal G, et al. Adaptation to host specific bacterial pathogens drive rapid evolution of novel PhoP/PhoQ regulation pathway modulating the virulence. Microb. Pathog. 2020; 141: 103997. Disponible en: https://doi.org/10.1016/j.micpath.2020.103997Cao L, Wang J, Sun L, Kong Z, Wu Q, Wang Z, et al. Transcriptional analysis reveals the relativity of acid tolerance and antimicrobial peptide resistance of Salmonella. Microb. Pathog. 2019; 136: 103701. Disponible en: https://doi.org/10.1016/j.micpath.2019.103701Tsai M, Liang Y, Chen C, Chiu C. Characterization of Salmonella resistance to bile during biofilm formation. J Microbiol Immunol Infect. 2020; 53 (4): 518-524. Disponible en: https://doi.org/10.1016/j.jmii.2019.06.003Gunn J, Richards S. Recognition and Integration of Multiple Environmental Signals by the Bacterial Sensor Kinase PhoQ. Cell Host Microbe. 2007; 1 (3): 163-165. Disponible en: https://www.cell.com/fulltext/S1931-3128(07)00075-3Prost L, Daley M, Sage V, Bader M, Moual H, Klevit R, et al. Activation of the Bacterial Sensor Kinase PhoQ by Acidic pH. Mol. cell. 2007; 26 (2): 165-174. Disponible en: https://www.sciencedirect.com/science/article/pii/S1097276507001530#:~:text=Suma ry,transcriptional%20program%20essential%20for%20virulence.&text=PhoQ%2 also%20binds%20and%20is,sensor%20domain%20to%20pH%205.5Carabajal M, Asquith C, Laitinen T, Tizzard G, Yim L, Rial A, et al. Quinazoline Based Antivirulence Compounds Selectively Target Salmonella PhoP/PhoQ Signal Transduction System. mBio. 2020; 64 (1): e01744-19. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187569/Liu L, Zheng S. Transcriptional regulation of Yersinia pestis biofilm formation. Microb. Pathog. 2019; 131: 212-217. Disponible en: https://doi.org/10.1016/j.micpath.2019.04.011Erickson D, Russel C, Johnson K, Hileman T, Steward R. PhoP and OxyR transcriptional regulators contribute to Yersinia pestis virulence and survival within Galleria mellonella. Microb. Pathog. 2011; 51 (6): 389-395. Disponible en: https://doi.org/10.1016/j.micpath.2011.08.008Bozue J, Mou S, Moody K, Cote C, Trevino S, Fritz D, Worsham P. The role of the phoPQ operon in the pathogenesis of the fully virulent CO92 strain of Yersinia pestis and the IP32953 strain of Yersinia pseudotuberculosis. Microb. Pathog. 2011; 50 (6): 314-321. Disponible en: https://doi.org/10.1016/j.micpath.2011.02.005Lin Z, Cai X, Chen M, Ye L, Wu Y, Wang X, et al. Virulence and Stress Responses of Shigella flexneri Regulated by PhoP/PhoQ. Front. Microbiol. 2018; 8:2689. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775216/Nakka S, Qi M, Zhao Y. The Erwinia amylovora PhoPQ system is involved in resistance to antimicrobial peptide and suppresses gene expression of two novel type III secretion systems. Microbiol. Res. 2010; 165 (8): 665-673. Disponible en: https://www.sciencedirect.com/science/article/pii/S0944501309001165?via%3DihubSerra M. La resistencia microbiana en el contexto actual y la importancia del conocimiento y aplicación en la política antimicrobiana. Rev haban cienc méd. 2017; 16 (3): 1729-519. Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1729519X20170003 00011ISGLOBAL. Los 4 frentes de batalla contra la resistencia a los antibióticos. [Internet]. Disponible en: https://www.isglobal.org/informe-la-batalla-contra-las-resistencias [Consultado el 30 de enero de 2020]Pintilie L, Stefaniu A. In Silico Drug Design and Molecular Docking Studies of Some Quinolone Compound. Molecular Docking and Molecular Dynamics. 2019. Disponible en: https://www.intechopen.com/books/molecular-docking-and-molecular-dynamics/-em-i n-silico-em-drug-design-and-molecular-docking-studies-of-some-quinolone-compoun dJeukens J, Freschi J, Kukavica‐Ibrulj I, Emond J, Tucker N & Levesque R. Genomics of antibiotic‐resistance prediction in Pseudomonas aeruginosa. Ann N Y Acad Sci. 2019; 1435(1): 5–17. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379567/Soukarieh F, Vico E, Dubern J, Gomes J, Halliday N, Crespo M, et al. In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa. Molecules. 2018; 23(2): 257. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017655/Solanki V, Tiwari M & Tiwari V. Prioritization of potential vaccine targets using comparative proteomics and designing of the chimeric multi-epitope vaccine against Pseudomonas aeruginosa. Sci Rep. 2019; 9: 5240. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437148/National Center for Biotechnology Information (NCBI). Basic Local Alignment Search Tool (BLAST). Disponible en: https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastn&PAGE_TYPE=B lastSearch&BLAST_SPEC=&LINK_LOC=blasttab&LAS T_PAGE=blastpMEGA. Disponible en: https://www.megasoftware.net/Khan S. Árboles filogenéticos. [Internet]. Khan Academy. 2016. [citado 20 de mayo del 2021]. Disponible en: https://es.khanacademy.org/science/high-schoolbiology/hs-evolution/hs-phylogeny/a/ phylogenetic-treesMartínez-Lage, A y González-Tizón, A. Aplicaciones de la bioinformática en la elaboración de filogenias moleculares. 2004. Fundación Alfredo Brañas. 53-81. Disponible en: https://www.udc.es/grupos/gibe/uploads/gibe/andres%20ana/filogenias.pdfNei M & Kumar S. Molecular Evolution and Phylogenetics. 1 ed. New York: Oxford University Press: 2000.Protparam tool. Disponible en: https://web.expasy.org/protparam/PROSITE Database of protein domains, families and functional sites. Disponible en: https://prosite.expasy.org/SWISS-MODEL. Disponible en: https://swissmodel.expasy.org/PSIPRED. Disponible en: http://bioinf.cs.ucl.ac.uk/psipred/GOR IV. Disponible en: https://npsaprabi.ibcp.fr/cgibin/npsa_automat.pl?page=/NPSA/npsa_gor4.htmlProtein Structure Analisis Web. Disponible en: https://prosa.services.came.sbg.ac.at/prosa.phpJochumsen N, Marvig R, Damkkiaer S, Lyngkli p R, Paulander W, Molin S, et al. The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is shaped by strong epistatic interactions. Nat. Commun. 2016; 7: 13002. Disponible en: https://www.nature.com/articles/ncomms13002Barrow K, Know D. Alterations in Two-Component Regulatory Systems of phoPQ and pmrAB Are Associated with Polymyxin B Resistance in Clinical Isolates of Pseudomonas aeruginosa. J. Clin. Microbiol. 2020; 53 (12). Disponible en: https://journals.asm.org/doi/10.1128/AAC.00893-09Meng L, Liu H, Lan T, Dong L, Hu H, Zhao S, et al. Antibiotic Resistance Patterns of Pseudomonas spp. Isolated From Raw Milk Revealed by Whole Genome Sequencing. Front. Microbiol. 2020; 11:1005. Disponible en: https://www.frontiersin.org/articles/10.3389/fmicb.2020.01005/fullGutu A, Sgambati N, Strasbourger P, Brannon M, Jacobs M, Haugen E, et al. Polymyxin Resistance of Pseudomonas aeruginosa phoQ Mutants Is Dependent on Additional Two-Component Regulatory Systems. J. Clin. Microbiol. 2013; 57 (5). Disponible en: https://journals.asm.org/doi/10.1128/aac.02353-12?permanently=trueGooderham J, Hancock R. Regulation of virulence and antibiotic resistance by two-component regulatory systems in Pseudomonas aeruginosa. FEMS Microbiology Reviews. 2009; 33 (2): 279-294. Disponible en: https://academic.oup.com/femsre/article/33/2/279/588178Olaitan A, Morand S, Rolain J. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front. Microbiol. 2014; 5:643.Disponible en: https://www.frontiersin.org/articles/10.3389/fmicb.2014.00643/fullMiller A, Brannon M, Stevens L, Krogh H, Selgrade S, Miller S, et al. PhoQ Mutations Promote Lipid A Modification and Polymyxin Resistance of Pseudomonas aeruginosa Found in Colistin-Treated Cystic Fibrosis Patients. Antimicrob Agents Chemother. 2011; 55(12): 5761–5769. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232818/Molina L, Udaondo Z, Duque E, Fernández M, Molina M, Roca A, et al. Antibiotic Resistance Determinants in a Pseudomonas putida Strain Isolated from a Hospital. PloS one. 2014. Disponible en: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081604Macfarlane E, Kwasnicka A, Ochs M, Hancock R. PhoP–PhoQ homologues in Pseudomonas aeruginosa regulate expression of the outer-membrane protein OprH and polymyxin B resistance. Mol. Microbiol. 2002; 34 (2): 305-316. Disponible en: https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2958.1999.01600.Francis V, Stevenson E, Porter S. Two-component systems required for virulence in Pseudomonas aeruginosa. FEMS Microbiol Lett. 2017; 364(11): fnx104. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812489/McPhee K, Lewenza S, Hanckock R. Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa. Mol. Microbiol. 2003; 50 (1): 205-217. Disponible en: https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2958.2003.03673.xMcPhee J, Bains M, Winsor G, Lewenza S, Brazas M, Brinkman F, et al. Contribution of the PhoP-PhoQ and PmrA-PmrB Two-Component Regulatory Systems to Mg2+-Induced Gene Regulation in Pseudomonas aeruginosa. J Bacteriol. 2006; 188(11): 3995–4006. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1482896/Olaitan A, Morand S, Rolain J. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front. Microbiol. 2014; 5:643. Disponible en: https://www.frontiersin.org/articles/10.3389/fmicb.2014.00643/fullProst L, Daley M, Bader M, Klevit Miller S. The PhoQ Histidine Kinases of Salmonella and Pseudomonas spp. are Structurally and Functionally Different: Evidence that pH and Antimicrobial Peptide Sensing Contribute to Mammalian Pathogenesis. Mol Microbiol. 2008; 69(2): 503–519. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2555970/Gunn J. The Salmonella PmrAB regulon: lipopolysaccharide modifications, antimicrobial peptide resistance and more. Trends Microbiol. 2008; 16 (6): 284-290. Disponible en: https://sci-hub.se/https://doi.org/10.1016/j.tim.2008.03.007Gellatly S. Regulation of the PhoQ-PhoP two-component system in Pseudomonas aeruginosa and its role in virulence. [Doctoral]. University of Victoria; 2012.Brinkman F, MacFarlane E, Warrener P, Hancock R. Evolutionary Relationships among Virulence-Associated Histidine Kinases. Infect Immun. 2001; 69(8): 5207–5211. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC98623/Molnar K, Bonomi M, Pellarin R, Clinthorne G, Gonzalez G, Goldberg S, et al. Cys-scanning Disulfide crosslinking and Bayesian modeling probe the transmembrane signaling mechanism of the histidine kinase, PhoQ. Structure. 2014; 22(9): 1239–1251. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322757Lesley J, Waldburger C. Comparison of the Pseudomonas aeruginosa andEscherichia coli PhoQ Sensor Domains. J. Biol. Chem. 2001; 276 (33): P30827- 30833. Disponible en: https://www.jbc.org/article/S0021-9258(20)80227-/fulltext#fig1Matamouros S, Hager K, Miller S. HAMP Domain Rotation and Tilting Movements Associated with Signal Transduction in the PhoQ Sensor Kinase. mBio. 2015; 6(3): e00616. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447245/Stock A, Robinson V, Goudreau P. Two-Component Signal Transduction. Biochemistry. 2000; 69:183-215. Disponible en: https://www.annualreviews.org/doi/10.1146/annurev.biochem.69.1.183Velikova N, Fulle S, Manso A, Mechkarska M, Finn P, Conlon J, et al. Putative histidine kinase inhibitors with antibacterial effect against multi-drug resistant clinical isolates identified by in vitro and in silico screens. Sci Rep. 2016; 6: 26085. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865847/Viarengo G. Identificación y caracterización de compuestos antibacterianos a partir de productos naturales o semisintéticos. [Doctoral]. Universidad Nacional del Litoral; 2015.Cheung J, Hendrickson W. Sensor Domains of Two-Component Regulatory Systems. Curr Opin Microbiol. 2010; 13(2): 116–123. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078554/Ahmad A, Fadel F, Kreuzer C, Ba M, Pélissier G, Bornet O, et al. Structural and functional insights into the periplasmic detector domain of the GacS histidine kinase controlling biofilm formation in Pseudomonas aeruginosa. Sci Rep. 2017; 7: 11262. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595915/SensibilidadMDRPseudomonas aeruginosaSistema de dos componentesPhoQTEXTFORMATO CARTA DERECHOS DE AUTOR FIRMA DECANA IIP2021 Rodriguez.docx.pdf.txtFORMATO CARTA DERECHOS DE AUTOR FIRMA DECANA IIP2021 Rodriguez.docx.pdf.txtExtracted texttext/plain1079https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/8/FORMATO%20CARTA%20DERECHOS%20DE%20AUTOR%20FIRMA%20DECANA%20IIP2021%20Rodriguez.docx.pdf.txt0dc9aed7f7ae83ef28db96afadb50d6eMD58metadata only accessSustentación proyecto de grado 2021 Rodriguez Vasquez.pptx.txtSustentación proyecto de grado 2021 Rodriguez Vasquez.pptx.txtExtracted texttext/plain12801https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/10/Sustentaci%c3%b3n%20proyecto%20de%20grado%202021%20Rodriguez%20Vasquez.pptx.txtde31de11e15f13cf870f4411ba3ea702MD510metadata only accessCaracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR).docx.pdf.txtCaracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR).docx.pdf.txtExtracted texttext/plain121290https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/11/Caracterizaci%c3%b3n%20in%20silico%20de%20los%20genes%20de%20virulencia%20PhoP%20-PhoQ%20en%20cepas%20de%20Pseudomonas%20aeruginosa%20fenotipo%20multidrogo-resistente%20%28MDR%29.docx.pdf.txt9c6b6f5db10c3b4d2c5ee8fea17f0885MD511open accessPORTADA TRABAJOS DE GRADO IIP 2021-LAURA RODRIGUEZ.docx.pdf.txtPORTADA TRABAJOS DE GRADO IIP 2021-LAURA RODRIGUEZ.docx.pdf.txtExtracted texttext/plain653https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/13/PORTADA%20TRABAJOS%20DE%20GRADO%20IIP%202021-LAURA%20RODRIGUEZ.docx.pdf.txt356279c86b9467d9140927296db29da2MD513metadata only accessFORMATO DERECHOS DE AUTOR TG 2021 -LAURA RODRIGUEZ.doc.pdf.txtFORMATO DERECHOS DE AUTOR TG 2021 -LAURA RODRIGUEZ.doc.pdf.txtExtracted texttext/plain1298https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/15/FORMATO%20DERECHOS%20DE%20AUTOR%20TG%202021%20-LAURA%20RODRIGUEZ.doc.pdf.txt4b113bdf9ec14ff1a1c6d5b4d6ee5b4aMD515metadata only accessCARTA DECANO DERECHOS DE AUTOR MODALIDADES DE GRADO IIP 2021.pdf.txtCARTA DECANO DERECHOS DE AUTOR MODALIDADES DE GRADO IIP 2021.pdf.txtExtracted texttext/plain1539https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/17/CARTA%20DECANO%20DERECHOS%20DE%20AUTOR%20MODALIDADES%20DE%20GRADO%20IIP%202021.pdf.txt15c691b6fdeaef1bc6d123286851a1f8MD517metadata only accessTHUMBNAILFORMATO CARTA DERECHOS DE AUTOR FIRMA DECANA IIP2021 Rodriguez.docx.pdf.jpgFORMATO CARTA DERECHOS DE AUTOR FIRMA DECANA IIP2021 Rodriguez.docx.pdf.jpgGenerated Thumbnailimage/jpeg9677https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/9/FORMATO%20CARTA%20DERECHOS%20DE%20AUTOR%20FIRMA%20DECANA%20IIP2021%20Rodriguez.docx.pdf.jpg13d0e8df2bfb95a17ed466f5220a9c26MD59metadata only accessCaracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR).docx.pdf.jpgCaracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR).docx.pdf.jpgGenerated Thumbnailimage/jpeg6128https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/12/Caracterizaci%c3%b3n%20in%20silico%20de%20los%20genes%20de%20virulencia%20PhoP%20-PhoQ%20en%20cepas%20de%20Pseudomonas%20aeruginosa%20fenotipo%20multidrogo-resistente%20%28MDR%29.docx.pdf.jpgef7d0ffff8f88966cb243bc85cb695deMD512open accessPORTADA TRABAJOS DE GRADO IIP 2021-LAURA RODRIGUEZ.docx.pdf.jpgPORTADA TRABAJOS DE GRADO IIP 2021-LAURA RODRIGUEZ.docx.pdf.jpgGenerated Thumbnailimage/jpeg7998https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/14/PORTADA%20TRABAJOS%20DE%20GRADO%20IIP%202021-LAURA%20RODRIGUEZ.docx.pdf.jpg0e501bac6d0157891856cd06ae4ed127MD514metadata only accessFORMATO DERECHOS DE AUTOR TG 2021 -LAURA RODRIGUEZ.doc.pdf.jpgFORMATO DERECHOS DE AUTOR TG 2021 -LAURA RODRIGUEZ.doc.pdf.jpgGenerated Thumbnailimage/jpeg12033https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/16/FORMATO%20DERECHOS%20DE%20AUTOR%20TG%202021%20-LAURA%20RODRIGUEZ.doc.pdf.jpgadf149ec9a903f76dc0085b754de0599MD516metadata only accessCARTA DECANO DERECHOS DE AUTOR MODALIDADES DE GRADO IIP 2021.pdf.jpgCARTA DECANO DERECHOS DE AUTOR MODALIDADES DE GRADO IIP 2021.pdf.jpgGenerated Thumbnailimage/jpeg9846https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/18/CARTA%20DECANO%20DERECHOS%20DE%20AUTOR%20MODALIDADES%20DE%20GRADO%20IIP%202021.pdf.jpga0b679346419d6b2cfdc9d604a17cf4aMD518metadata only accessLICENSElicense.txtlicense.txttext/plain; charset=utf-814828https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/7/license.txt2f9959eaf5b71fae44bbf9ec84150c7aMD57open accessORIGINALCaracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR).docx.pdfCaracterización in silico de los genes de virulencia PhoP -PhoQ en cepas de Pseudomonas aeruginosa fenotipo multidrogo-resistente (MDR).docx.pdfapplication/pdf2940005https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/19/Caracterizaci%c3%b3n%20in%20silico%20de%20los%20genes%20de%20virulencia%20PhoP%20-PhoQ%20en%20cepas%20de%20Pseudomonas%20aeruginosa%20fenotipo%20multidrogo-resistente%20%28MDR%29.docx.pdf9095ef5a6c544b9579854364017f5dafMD519open accessSustentación proyecto de grado 2021 Rodriguez Vasquez.pptxSustentación proyecto de grado 2021 Rodriguez Vasquez.pptxapplication/vnd.openxmlformats-officedocument.presentationml.presentation12809297https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/20/Sustentaci%c3%b3n%20proyecto%20de%20grado%202021%20Rodriguez%20Vasquez.pptx3372e9dac5ca2adb0fc8976766d7dfdfMD520open accessFORMATO CARTA DERECHOS DE AUTOR FIRMA DECANA IIP2021 Rodriguez.docx.pdfFORMATO CARTA DERECHOS DE AUTOR FIRMA DECANA IIP2021 Rodriguez.docx.pdfapplication/pdf108722https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/21/FORMATO%20CARTA%20DERECHOS%20DE%20AUTOR%20FIRMA%20DECANA%20IIP2021%20Rodriguez.docx.pdff52385d980521fc923b51bef80471042MD521metadata only accessFORMATO DERECHOS DE AUTOR TG 2021 -LAURA RODRIGUEZ.doc.pdfFORMATO DERECHOS DE AUTOR TG 2021 -LAURA RODRIGUEZ.doc.pdfapplication/pdf156117https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5553/22/FORMATO%20DERECHOS%20DE%20AUTOR%20TG%202021%20-LAURA%20RODRIGUEZ.doc.pdf1a32bc978374f030af469b27747ffb21MD522metadata only accessunicolmayor/5553oai:repositorio.unicolmayor.edu.co:unicolmayor/55532024-05-02 10:34:53.724An error occurred on the license name.|||https://creativecommons.org/licenses/by-nc-sa/4.0/open accessBiblioteca Digital Unicolmayorrepositorio@unicolmayor.edu.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

Publicaciones similares