Actividad antibacteriana del péptido LfcinB (20-25)4 contra aislados clínicos multirresistentes de E. coli Y S. aureus
Texto
- Autores:
-
Bonilla Velásquez, Laura Daniela
- Tipo de recurso:
- Fecha de publicación:
- 2021
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/79982
- Palabra clave:
- 610 - Medicina y salud::615 - Farmacología y terapéutica
Antibacterianos
Anti-Bacterial Agents
Enfermedades transmisibles
Communicable Diseases
Lactoferricina Bovina
Actividad antibacteriana
Aislados clínicos
Multirresistentes
Péptidos antimicrobianos
Bovine lactoferricin
Antibacterial activity
Clinical isolates
Antimicrobial peptides
- Rights
- openAccess
- License
- Reconocimiento 4.0 Internacional
| id |
UNACIONAL2_8f572b8e1051deee2fa773da84df10a9 |
|---|---|
| oai_identifier_str |
oai:repositorio.unal.edu.co:unal/79982 |
| network_acronym_str |
UNACIONAL2 |
| network_name_str |
Universidad Nacional de Colombia |
| repository_id_str |
|
| dc.title.spa.fl_str_mv |
Actividad antibacteriana del péptido LfcinB (20-25)4 contra aislados clínicos multirresistentes de E. coli Y S. aureus |
| dc.title.translated.eng.fl_str_mv |
Antibacterial activity of the LfcinB (20-25) 4 peptide against multi-resistant clinical isolates of E. coli and S. aureus |
| title |
Actividad antibacteriana del péptido LfcinB (20-25)4 contra aislados clínicos multirresistentes de E. coli Y S. aureus |
| spellingShingle |
Actividad antibacteriana del péptido LfcinB (20-25)4 contra aislados clínicos multirresistentes de E. coli Y S. aureus 610 - Medicina y salud::615 - Farmacología y terapéutica Antibacterianos Anti-Bacterial Agents Enfermedades transmisibles Communicable Diseases Lactoferricina Bovina Actividad antibacteriana Aislados clínicos Multirresistentes Péptidos antimicrobianos Bovine lactoferricin Antibacterial activity Clinical isolates Antimicrobial peptides |
| title_short |
Actividad antibacteriana del péptido LfcinB (20-25)4 contra aislados clínicos multirresistentes de E. coli Y S. aureus |
| title_full |
Actividad antibacteriana del péptido LfcinB (20-25)4 contra aislados clínicos multirresistentes de E. coli Y S. aureus |
| title_fullStr |
Actividad antibacteriana del péptido LfcinB (20-25)4 contra aislados clínicos multirresistentes de E. coli Y S. aureus |
| title_full_unstemmed |
Actividad antibacteriana del péptido LfcinB (20-25)4 contra aislados clínicos multirresistentes de E. coli Y S. aureus |
| title_sort |
Actividad antibacteriana del péptido LfcinB (20-25)4 contra aislados clínicos multirresistentes de E. coli Y S. aureus |
| dc.creator.fl_str_mv |
Bonilla Velásquez, Laura Daniela |
| dc.contributor.advisor.none.fl_str_mv |
Rivera Monroy, Zuly Jenny Parra Giraldo, Claudia Marcela |
| dc.contributor.author.none.fl_str_mv |
Bonilla Velásquez, Laura Daniela |
| dc.contributor.researchgroup.spa.fl_str_mv |
Síntesis y aplicación de moléculas peptídicas |
| dc.subject.ddc.spa.fl_str_mv |
610 - Medicina y salud::615 - Farmacología y terapéutica |
| topic |
610 - Medicina y salud::615 - Farmacología y terapéutica Antibacterianos Anti-Bacterial Agents Enfermedades transmisibles Communicable Diseases Lactoferricina Bovina Actividad antibacteriana Aislados clínicos Multirresistentes Péptidos antimicrobianos Bovine lactoferricin Antibacterial activity Clinical isolates Antimicrobial peptides |
| dc.subject.decs.none.fl_str_mv |
Antibacterianos Anti-Bacterial Agents Enfermedades transmisibles Communicable Diseases |
| dc.subject.proposal.spa.fl_str_mv |
Lactoferricina Bovina Actividad antibacteriana Aislados clínicos Multirresistentes Péptidos antimicrobianos |
| dc.subject.proposal.eng.fl_str_mv |
Bovine lactoferricin Antibacterial activity Clinical isolates Antimicrobial peptides |
| description |
Texto |
| publishDate |
2021 |
| dc.date.accessioned.none.fl_str_mv |
2021-08-20T15:36:37Z |
| dc.date.available.none.fl_str_mv |
2021-08-20T15:36:37Z |
| dc.date.issued.none.fl_str_mv |
2021-05-30 |
| dc.type.spa.fl_str_mv |
Trabajo de grado - Maestría |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/masterThesis |
| dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
| dc.type.content.spa.fl_str_mv |
Text |
| dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/TM |
| status_str |
acceptedVersion |
| dc.identifier.uri.none.fl_str_mv |
https://repositorio.unal.edu.co/handle/unal/79982 |
| dc.identifier.instname.spa.fl_str_mv |
Universidad Nacional de Colombia |
| dc.identifier.reponame.spa.fl_str_mv |
Repositorio Institucional Universidad Nacional de Colombia |
| dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.unal.edu.co/ |
| url |
https://repositorio.unal.edu.co/handle/unal/79982 https://repositorio.unal.edu.co/ |
| identifier_str_mv |
Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia |
| dc.language.iso.spa.fl_str_mv |
spa |
| language |
spa |
| dc.relation.references.spa.fl_str_mv |
Inoue H, Minghui R. Antimicrobial resistance: Translating political commitment into national action. Bull World Health Organ. 2017;95(4):242- 242A. Shrivastava SR, Shrivastava PS, Ramasamy J. World health organization releases global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. JMS - J Med Soc. 2018;32(1):76–7. Exner M, Bhattacharya S, Christiansen B, Gebel J, Goroncy-Bermes P, Hartemann P, et al. Antibiotic resistance: What is so special about multidrug- resistant Gram-negative bacteria? GMS Hyg Infect Control [Internet]. 2017;12:Doc05. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28451516%0Ahttp://www.pubmedce ntral.nih.gov/articlerender.fcgi?artid=PMC5388835 Willyard C. The drug-resistant bacteria that pose the greatest health threats. Nature. 2017;543(7643):15. Aminov RI. A brief history of the antibiotic era: Lessons learned and challenges for the future. Front Microbiol. 2010;1(DEC):1–7. Blair JMA, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJV. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol [Internet]. 2015;13(1):42–51. Available from: http://dx.doi.org/10.1038/nrmicro3380 OMS. Resistencia a los antimicrobianos Situación actual Resistencia de las bacterias [Internet]. 2020. Available from: https://www.who.int/es/news- room/fact-sheets/detail/resistencia-a-los-antimicrobianos Grupo de Microbiología Subdirección Laboratorio Nacional de Referencia (SLNR). Infecciones asociadas a la atención en salud. Epidemiología de las infecciones asociadas a la atención en salud. 2019. Ministerio de Salud y Protección Social. Plan Nacional de Respuesta a la Resistencia a los Antimicrobianos - plan estratégico. 2018;66. Available from: https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/MET /plan-respuesta-resistencia-antimicrobianos.pdf Maldonado NA, Múnera MI, López JA, Sierra P, Robledo C, Robledo J, et al. Tendencias de la resistencia a antibióticos en Medellín y en los municipios del área metropolitana entre 2007 y 2012: Resultados de seis años de vigilancia. Biomedica. 2014;34(3):433–46. Chung PY, Khanum R. Antimicrobial peptides as potential anti-biofilm agents against multidrug-resistant bacteria. J Microbiol Immunol Infect [Internet]. 2017;50(4):405–10. Available from: http://dx.doi.org/10.1016/j.jmii.2016.12.005 Bahar AA, Ren D. Antimicrobial peptides. Pharmaceuticals. 2013;6(12):1543– 75. Rodríguez-Franco DA, Vázquez-Moreno L, Ramos-Clamont Montfort G. Actividad antimicrobiana de la lactoferrina: Mecanismos y aplicaciones clínicas potenciales. Rev Latinoam Microbiol. 2005;47(3–4):102–11. Murata M, Wakabayashi H, Yamauchi K, Abe F. Identification of milk proteins enhancing the antimicrobial activity of lactoferrin and lactoferricin. J Dairy Sci [Internet]. 2013;96(8):4891–8. Available from: http://dx.doi.org/10.3168/jds.2013-6612 L.Cheng-Foh FM, S.Shamala. Intracellular Targeting Mechanisms by antimicrobial peptides. 2017;61(4):1–16. Yamauchi K, Tomita M, Giehl TJ, Ellison RT. Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment. Infect Immun.1993;61(2):719–28. Vorland LH, Ulvatne H, Andersen J, Haukland HH, Rekdal Ø, Svendsen JS, et al. Lactoferricin of bovine origin is more active than lactoferricins of human, murine and caprine origin. Scand J Infect Dis. 1998;30(5):513–7. Sinha M, Kaushik S, Kaur P, Sharma S, Singh TP. Antimicrobial lactoferrin peptides: The hidden players in the protective function of a multifunctional protein. Int J Pept. 2013;2013(February 2015). Schibli DJ, Hwang PM, Vogel HJ. The structure of the antimicrobial active center of lactoferricin B bound to sodium dodecyl sulfate micelles. FEBS Lett. 1999;446(2–3):213–7. León-Calvijo MA, Leal-Castro AL, Almanzar-Reina GA, Rosas-Pérez JE, García-Castañeda JE, Rivera-Monroy ZJ. Antibacterial Activity of Synthetic Peptides Derived from Lactoferricin against Escherichia coli ATCC 25922 and Enterococcus faecalis ATCC 29212. Biomed Res Int. 2015 Mar;2015:1–8. Huertas N de J, Monroy ZJR, Medina RF, Castañeda JEG. Antimicrobial Activity of Truncated and Polyvalent Peptides Derived from the FKCRRQWQWRMKKGLA Sequence against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. Molecules. 2017;22(6). Vargas Casanova Y, Rodríguez Guerra JA, Umaña Pérez YA, Leal Castro AL, Almanzar Reina G, García Castañeda JE, et al. Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB- 468 and MDA-MB-231 Breast Cancer Cell Lines. Molecules. 2017;22(10):1–11. Vargas-Casanova Y, Rodríguez-Mayor AV, Cardenas KJ, Leal-Castro AL, Muñoz-Molina LC, Fierro-Medina R, et al. Synergistic bactericide and antibiotic effects of dimeric, tetrameric, or palindromic peptides containing the RWQWR motif against Gram-positive and Gram-negative strains. RSC Adv. 2019;9(13):7239–45. Alby K, Miller MB. Mechanisms and Detection of Antimicrobial Resistance [Internet]. Fifth Edit. Principles and Practice of Pediatric Infectious Diseases. Elsevier Inc.; 2017. 1467-1478.e4 p. Available from: http://dx.doi.org/10.1016/B978-0-323-40181-4.00290-5 Theuretzbacher U. Global antibacterial resistance: The never-ending story. J Glob Antimicrob Resist [Internet]. 2013;1(2):63–9. Available from: http://dx.doi.org/10.1016/j.jgar.2013.03.010 Gómez Rubio A. Consumo de antibióticos en el ámbito hospitalario en Colombia, primer semestre de 2019. Inst Nac Salud. 2019;1–16. Afacan NJ, Yeung ATY, Pena OM, Hancock REW. Therapeutic potential of host defense peptides in antibiotic-resistant infections. Curr Pharm Des [Internet]. 2012;18(6):807–19. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22236127 Germán Alberto Téllez1, Jhon Carlos Castaño1. Péptidos antimicrobianos Antimicrobial peptides. 2010;14(1):55–67. Available from: www.ncbi.nlm.nih.gov/pubmed Rana M, Chatterjee S, Kochhar S, Pereira BMJ. Antimicrobial Peptides: a New Dawn for Regulating Fertility and Reproductive Tract Infections. J Endocrinol Reprod [Internet]. 2006;2:88–95. Available from: http://srbce.org/journal12b/002.pdf Bellamy W, Takase M, Wakabayashi H, Kawase K, Tomita M. Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N‐terminal region of bovine lactoferrin. J Appl Bacteriol. 1992;73(6):472–9. Schiffer M, Chang CH, Stevens FJ. The functions of tryptophan residues in membrane proteins. Protein Eng Des Sel. 1992;5(3):213–4. De Jesus AJ, Allen TW. The role of tryptophan side chains in membrane protein anchoring and hydrophobic mismatch. Biochim Biophys Acta - Biomembr [Internet]. 2013;1828(2):864–76. Available from: http://dx.doi.org/10.1016/j.bbamem.2012.09.009 Vorland LH, Osbakk SA, Perstølen T, Ulvatne H, Rekdal Ø, Svendsen JS, et al. Interference of the antimicrobial peptide lactoferricin B with the action of various antibiotics against Escherichia coli and Staphylococcus aureus. Scand J Infect Dis. 1999;31(2):173–7. Feng X jun, Wang J hua, Shan A shan, Teng D, Yang Y lin, Yao Y, et al. Fusion expression of bovine lactoferricin in Escherichia coli. Protein Expr Purif. 2006;47(1):110–7. Vargas Casanova Y. Evaluación De La Actividad Antibacteriana De Péptidos Diméricos Y Tetraméricos Derivados De Lactoferricina Bovina Contra Bacterias Gram Positivas Y Gram Negativas. Universidad Nacional de Colombia; 2018. Huertas Méndez NDJ, Vargas Casanova Y, Gómez Chimbi AK, Hernández E, Leal Castro AL, Melo Diaz JM, et al. Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Antimicrobial Activity against E. coli ATCC 11775, S. maltophilia ATCC 13636 and S. enteritidis ATCC 13076. Molecules. 2017;22(3):1–10. Sinha M, Kaushik S, Kaur P, Sharma S, Singh TP. Antimicrobial lactoferrin peptides: The hidden players in the protective function of a multifunctional protein. Int J Pept. 2013;2013. Gifford JL, Hunter HN, Vogel HJ. Lactoferricin: A lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties. CellMol Life Sci. 2005;62(22):2588–98. Ptaszyńska N, Olkiewicz K, Okońska J, Gucwa K, Łęgowska A, Gitlin-Domagalska A, et al. Peptide conjugates of lactoferricin analogues and antimicrobials—Design, chemical synthesis, and evaluation of antimicrobial activity and mammalian cytotoxicity. Peptides [Internet]. 2019;117(March):170079. Available from: https://doi.org/10.1016/j.peptides.2019.04.006 Farnaud S, Spiller C, Moriarty LC, Patel A, Gant V, Odell EW, et al. Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity. FEMS Microbiol Lett. 2004;233(2):193–9. Vega SC, Martínez DA, Chalá M del S, Vargas HA, Rosas JE. Design, synthesis and evaluation of branched RRWQWR-based peptides as antibacterial agents against clinically relevant gram-positive and gram-negative pathogens. Front Microbiol. 2018;9(MAR). Vega Chaparro SC, Valencia Salguero JT, Martínez Baquero DA, Rosas Pérez JE. Effect of Polyvalence on the Antibacterial Activity of a Synthetic Peptide Derived from Bovine Lactoferricin against Healthcare-Associated Infectious Pathogens. Biomed Res Int. 2018;2018. Concepción Porrero Calonge. Detección y caracterización de Staphylococcus aureus procedentes de aninales y aguas. Universidad Complutense de Madrid; 2014. Borraz Ordás C. Epidemiología De La Resistencia a Meticilina [Internet].Universidad de barcelona; 2003. Available from: http://www.tdx.cat/bitstream/handle/10803/2513/CBO_TESIS_DOCTORAL.pdf Davies J, Davies D. Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev. 2010;74(3):417–33. Leal-Castro AL, Álvarez CA. Resultados de la vigilancia de la resistencia bacteriana. 2019. Lacueva Arnedo M. Resistencia a antibióticos en Staphylococcus aureus. Evolución y perspectiva actual [Internet]. Universidad complutense; 2017. Available from: https://eprints.ucm.es/54765/ Zhang HZ, Hackbarth CJ, Chansky KM, Chambers HF. A proteolytic transmembrane signaling pathway and resistance to β-lactams in staphylococci. Science (80- ). 2001;291(5510):1962–5. Shajari G, Khorshidi A, Moosavi G. Vancomycin resistance in Staphylococcus aureus strains. Arch Razi Inst. 2017;90(54):107–10. Araos R, García P, Chanqueo L, Labarca J. Daptomycin: Pharmacological characteristics and its role in the treatment of gram positive infections. Rev Chil Infectología. 2012;29(2):127–31. Casanova, Natalia Gómez, María, Siller Ruiz JLMB. Mechanisms of resistance to Daptomycin in Staphylococcus aureus. Kasmera [Internet]. 2010;38(6):36–44. Available from: http://seq.es/wp- content/uploads/2017/12/gomez25oct2017.pdf Velasco C de caceres. Evolución de la resistencia a antibióticos en Staphylococcus aureus . Universidad Complutense; 2016. Ruiz Larrea F, Lantero M, Torres Gómez C, Portillo A, Zarazaga Chamorro M, Olarte I, et al. Resistencia a antibióticos macrólidos-lincosamidas- estreptograminas y mecanismos implicados en cepas clínicas de “Streptococcus” spp. en La Rioja. Zubía. 2000;12(12):11–26. McCallum N, Berger-Bächi B, Senn MM. Regulation of antibiotic resistance in Staphylococcus aureus. Int J Med Microbiol. 2010;300(2–3):118–29. Benito Pascual D. Líneas genéticas, virulencia y resistencia a antibióticos en Staphylococcus aureus de diferentes orígenes. Análisis de marcadores de adaptación al huésped y comportamiento en Caenorhabditis elegans. Universidad de la Rioja; 2015. Truong-Bolduc QC, Dunman PM, Strahilevitz J, Projan SJ, Hooper DC. MgrA is a multiple regulator of two new efflux pumps in Staphylococcus aureus. J Bacteriol. 2005;187(7):2395–405. Romeu B. Caracterización de cepas de Escherichia coli de importancia clínica humana aisladas de ecosistemas dulceacuícolas de La Habana. Repositorio de Tesis Universidad de La Habana. 2012. Grupo de evaluación de riesgos de inocuidad de Alimentos. Perfil de riesgo de Escherichia coli enterotoxigénica y verotoxigénica en queso fresco [Internet]. Instituto Nacional de Salud. 2015. Available from: http://www.ghbook.ir/index.php?name option=com_dbook&task=readonline&book_id=13650&page=73&chkha&نوین shk=ED9C9491B4&Itemid=218&lang=fa&tmpl=component Alonso CA. Epidemiología molecular en Escherichia coli procedente de fauna salvaje : resistencia antimicrobiana , virulencia y diversidad y diversidad genética. Universidad de la Rioja; 2018. Vargas CRS. Elaboración y evaluación del material didáctico variedades enterovirulentas de Escherichia coli [Internet]. UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO; 2014. Available from: https://www.zaragoza.unam.mx/portal/wp- content/Portal2015/Licenciaturas/qfb/tesis/tesis_salas_vargas.pdf Gales AC, Castanheira M, Jones RN, Sader HS. Antimicrobial resistance among Gram-negative bacilli isolated from Latin America: Results from SENTRY Antimicrobial Surveillance Program (Latin America, 2008-2010). Diagn Microbiol Infect Dis [Internet]. 2012;73(4):354–60. Available from: http://dx.doi.org/10.1016/j.diagmicrobio.2012.04.007 García-Hernández AM, García-Vázquez E, Hernández-Torres A, Ruiz J, Yagüe G, Herrero JA, et al. Bacteraemia due to Escherichia coli producing extended-spectrum beta-lactamases (ESBL): clinical relevance and today’s insights. Rev Esp Quimioter [Internet]. 2011;24(2):57–66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21666996 Rice LB. Mechanisms of resistance and clinical relevance of resistance to β- lactams, glycopeptides, and fluoroquinolones. Mayo Clin Proc [Internet]. 2012;87(2):198–208. Available from: http://dx.doi.org/10.1016/j.mayocp.2011.12.003 Serra A. QUINOLONAS. Separata. 2008;16. Munita JM, Arias CA. Mechanisms of Antibiotic Resistance. Annu Rep Med Chem. 2016;4(2):119–27. Grünbaum F. Resistencia a aminoglucósidos en ENTEROBACTERIACEAE [Internet]. Universidad autónoma de Barcelona; 2011. Available from: http://www.tdx.cat/bitstream/handle/10803/42291/fg1de1.pdf?sequence=1 Maldonado N, Robledo C, Robledo J. La espectrometría de masas MALDI-TOF en el laboratorio de microbiología clínica. Infectio. 2018;22(1):35–45. Demirev P, Sandrin T. Aplications of mass spectrometry in microbiology. New York: Springer Cham Heidelberg; 2016. 1–336 p. Sampedro A, Ceballos Mendiola J, Aliaga Martínez L. MALDI-TOF Commercial Platforms for Bacterial Identification [Internet]. The Use of Mass Spectrometry Technology (MALDI-TOF) in Clinical Microbiology. Elsevier Inc.; 2018. 47–57 p. Available from: http://dx.doi.org/10.1016/B978-0-12- 814451-0.00003-4 Cramer R. Advances in MALDI and laser-induced soft ionization mass spectrometry. Adv MALDI Laser-Induced Soft Ioniz Mass Spectrom. 2015;1– 286. CLSI. M100 Performance Standards for Antimicrobial Susceptibility Testing [Internet]. Vol. 8, Journal of Services Marketing. 2019. 27–39 p. Available from: http://www.emeraldinsight.com/doi/10.1108/08876049410065598 Wiegand I, Hilpert K, Hancock REW. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc. 2008;3(2):163–75. Doern CD. When does 2 plus 2 equal 5? A review of antimicrobial synergy testing. J Clin Microbiol. 2014;52(12):4124–8. Vargas-Casanova Y. EVALUACIÓN DE LA ACTIVIDAD ANTIBACTERIANA DE PÉPTIDOS DIMÉRICOS Y TETRAMÉRICOS DERIVADOS DE LACTOFERRICINA BOVINA CONTRA BACTERIAS GRAM POSITIVAS Y GRAM NEGATIVAS. Universidad nacional de Colombia; 2018. Toledo MRF, Trabulsi LR. Correlation between biochemical and serological characteristics of Escherichia coli and results of the Sereny test. J Clin Microbiol. 1983;17(3):419–21. Park JJ, Seo Y Bin, Lee J. Antimicrobial susceptibilities of Enterobacteriaceae in community-acquired urinary tract infections during a 5-year period: A single hospital study in Korea. Infect Chemother. 2017;49(3):184–93. Ceballos-Garzón A, Cabrera E, Cortes-Fraile GC, León A, Aguirre-Guataqui K, Linares-Linares MY, et al. In-house protocol and performance of MALDI- TOF MS in the early diagnosis of bloodstream infections in a fourth-level hospital in Colombia: Jumping to full use of this technology. Int J Infect Dis. 2020;101:85–9. Bhat G, Bhat G. Atypical Escherichia Coli in Urinary Tract Infection. Trop Doct. 1995;25(3):127. Raksha R, Srinivasa H, Macaden RS. Occurrence and characterisation of Uropathogenic Escherichia coli in urinary tract infections. Indian J Med Microbiol [Internet]. 2003;21(2):102–7. Available from: https://doi.org/10.1016/S0255-0857(21)03130-3 T. R, M J. Prevalence of Atypical E . coli Causing Urinary Tract Infection in a Tertiary Care Hospital . Australas Med J. 2010;3(8):545–6. Bajpai T, Pandey M, Varma M, Bhatambare G. Importance of identification of lactose nonfermenting Escherichia coli and their prevalence in urinary isolates. CHRISMED J Heal Res. 2016;3(4):288. Kaczmarek A, Skowron K, Budzyńska A, Grudlewska K, Gospodarek- Komkowska E. Virulence genes and antimicrobial susceptibility of lactose- negative and lactose-positive strains of Escherichia coli isolated from pregnant women and neonates. Folia Microbiol (Praha). 2017;62(5):363–71. Chang J, Yu J, Lee H, Ryu H, Park K, Park YJ. Prevalence and characteristics of lactose non-fermenting Escherichia coli in urinary isolates. J Infect Chemother [Internet]. 2014;20(11):738–40. Available from: http://dx.doi.org/10.1016/j.jiac.2014.07.005 Hrabák J, Chudác ̌ková E, Walková R. Matrix-assisted laser desorption ionization-time of flight (MALDITOF) mass spectrometry for detection of antibiotic resistance mechanisms: From research to routine diagnosis. Clin Microbiol Rev. 2013;26(1):103–14. Ceballos-Garzon A, Amado D, Vélez N, Jiménez-A MJ, Rodríguez C, Parra- Giraldo CM. Development and validation of an in-house library of colombian candida auris strains with maldi-TOF MS to improve yeast identification. J Fungi. 2020;6(2):1–8. Sanguinetti M, Posteraro B. Mass spectrometry applications in microbiology beyond microbe identification: progress and potential. Expert Rev Proteomics. 2016;13(10):965–77. Kallow W, Erhard M, Shah H, Raptakis E, Welker M. MALDI - TOF MS for Microbial Identifi cation : Years of Experimental Development to an. In: Shah H, Gharbia S, editors. Mass Spectrometry for Microbial Proteomics. London; 2010. p. 255–76. 88. Dingle TC, Butler-Wu SM. MALDI-TOF mass spectrometry for microorganism identification. Clin Lab Med. 2013;33(3):589–609. Gil Gonzalo A. Espectrometría MALDI‐TOF aplicada a levaduras enológicas: identificación. [Internet]. Universidad de Valladolid; 2014. Available from: http://uvadoc.uva.es/bitstream/handle/10324/38124/TFG- G3567.pdf?sequence=1. Cipolla L, Rocca F, Armitano RI, Martinez C, Almuzara M, Faccone D, et al. Development and evaluation of an in-house database for quick identification of Burkholderia contaminans by MALDI-TOF MS. Rev Argent Microbiol [Internet]. 2019;51(3):255–8. Available from: https://doi.org/10.1016/j.ram.2018.09.001 Bou G, Fernández-Olmos A, García C, Sáez-Nieto JA, Valdezate S. Métodos de identificación bacteriana en el laboratorio de microbiología. Enferm Infecc Microbiol Clin. 2011;29(8):601–8. León-Calvijo MA, Leal-Castro AL, Almanzar-Reina GA, Rosas-Pérez JE, García-Castañeda JE, Rivera-Monroy ZJ. Antibacterial Activity of Synthetic Peptides Derived from Lactoferricin against Escherichia coli ATCC 25922 and Enterococcus faecalis ATCC 29212 . Biomed Res Int. 2015;2015:1–8. Flores-Villaseñor H, Canizalez-Román A, Reyes-Lopez M, Nazmi K, De La Garza M, Zazueta-Beltrán J, et al. Bactericidal effect of bovine lactoferrin, LFcin, LFampin and LFchimera on antibiotic-resistant Staphylococcus aureus and Escherichia coli. BioMetals. 2010;23(3):569–78. Pane K, Durante L, Crescenzi O, Cafaro V, Pizzo E, Varcamonti M, et al. Antimicrobial potency of cationic antimicrobial peptides can be predicted from their amino acid composition: Application to the detection of “cryptic” antimicrobial peptides. J Theor Biol [Internet]. 2017;419(January):254–65. Available from: http://dx.doi.org/10.1016/j.jtbi.2017.02.012 Yau WM, Wimley WC, Gawrisch K, White SH. The preference of tryptophan for membrane interfaces. Biochemistry. 1998;37(42):14713–8. Sun H, Greathouse D V., Andersen OS, Koeppe RE. The preference of tryptophan for membrane interfaces: Insights from N-methylation of tryptophans in gramicidin channels. J Biol Chem. 2008;283(32):22233–43. Wimley WC, White SH. Membrane Partitioning: Distinguishing Bilayer Effects from the Hydrophobic Effect. Biochemistry. 1993;32(25):6307–12. Chan DI, Prenner EJ, Vogel HJ. Tryptophan- and arginine-rich antimicrobial peptides: Structures and mechanisms of action. Biochim Biophys Acta - Biomembr. 2006;1758(9):1184–202. Haukland HH, Ulvatne H, Sandvik K, Vorland LH. The antimicrobial peptides lactoferricin B and magainin 2 cross over the bacterial cytoplasmic membrane and reside in the cytoplasm. FEBS Lett. 2001;508(3):389–93. Vergis J, Malik SS, Pathak R, Kumar M, Ramanjaneya S, Kurkure NV, et al. Exploiting Lactoferricin (17–30) as a Potential Antimicrobial and Antibiofilm Candidate Against Multi-Drug-Resistant Enteroaggregative Escherichia coli. Front Microbiol. 2020;11(September):1–13. Bonapace CR, Bosso JA, Friedrich L V., White RL. Comparison of methods of interpretation of checkerboard synergy testing. Diagn Microbiol Infect Dis. 2002;44(4):363–6. |
| dc.rights.spa.fl_str_mv |
Derechos reservados al autor, 2021 |
| dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
| dc.rights.license.spa.fl_str_mv |
Reconocimiento 4.0 Internacional |
| dc.rights.uri.spa.fl_str_mv |
http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.accessrights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
Reconocimiento 4.0 Internacional Derechos reservados al autor, 2021 http://creativecommons.org/licenses/by/4.0/ http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.extent.spa.fl_str_mv |
93 páginas |
| dc.format.mimetype.spa.fl_str_mv |
application/pdf |
| dc.publisher.spa.fl_str_mv |
Universidad Nacional de Colombia |
| dc.publisher.program.spa.fl_str_mv |
Bogotá - Ciencias - Maestría en Ciencias - Microbiología |
| dc.publisher.department.spa.fl_str_mv |
Instituto de Biotecnología (IBUN) |
| dc.publisher.faculty.spa.fl_str_mv |
Facultad de Ciencias |
| dc.publisher.place.spa.fl_str_mv |
Bogotá, Colombia |
| dc.publisher.branch.spa.fl_str_mv |
Universidad Nacional de Colombia - Sede Bogotá |
| institution |
Universidad Nacional de Colombia |
| bitstream.url.fl_str_mv |
https://repositorio.unal.edu.co/bitstream/unal/79982/1/license.txt https://repositorio.unal.edu.co/bitstream/unal/79982/2/1032464031.2021.pdf https://repositorio.unal.edu.co/bitstream/unal/79982/3/1032464031.2021.pdf.jpg |
| bitstream.checksum.fl_str_mv |
cccfe52f796b7c63423298c2d3365fc6 cdf97231b0f273e3bca22c9be1ea79d0 e24c49e7db344b8bf07e0e2b64c296be |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
| repository.name.fl_str_mv |
Repositorio Institucional Universidad Nacional de Colombia |
| repository.mail.fl_str_mv |
repositorio_nal@unal.edu.co |
| _version_ |
1814089799466745856 |
| spelling |
Reconocimiento 4.0 InternacionalDerechos reservados al autor, 2021http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Rivera Monroy, Zuly Jenny4d01a798fcb62ec5f5a8b8214fe50c7cParra Giraldo, Claudia Marcelaffcf6fc0b59f6bfe28c5a794cb7e41d1Bonilla Velásquez, Laura Danielacca9ae3bb310afd7b5e0ce7bfb97413aSíntesis y aplicación de moléculas peptídicas2021-08-20T15:36:37Z2021-08-20T15:36:37Z2021-05-30https://repositorio.unal.edu.co/handle/unal/79982Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/Textoilustraciones, gráficas, tablasLos péptidos antimicrobianos (PAMs) constituyen una alternativa terapéutica para el desarrollo de tratamientos de enfermedades infecciosas, que podrían contrarrestar el ascendente número de microorganismos resistentes a antibióticos que han incrementado el problema de salud pública a nivel mundial. La OMS en el año 2018, reportó la aparición de cepas resistentes y multirresistentes, bacterias como Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii y Staphylococcus aureus, han desarrollado mecanismos de resistencia frente a los antibióticos de primera línea, evidenciando la ineficacia de los fármacos utilizados comúnmente. Como una estrategia para ampliar las alternativas terapéuticas los péptidos derivados de la Lactoferricina Bovina (LfcinB), que contienen el motivo mínimo de actividad antimicrobiana RRWQWR, han sido evaluados contra cepas de referencia Gram positivas y Gram negativas, esta investigación ha permitido enfocar el péptido tetramérico LfcinB (20-25)4 con actividad antibacteriana promisoria. Dando continuidad a esta investigación, en el presente trabajo se evaluó la actividad antibacteriana de LfcinB (20-25)4 contra aislados clínicos de S. aureus y E. coli los cuales presentan diferentes perfiles de resistencia. Se determinó que el péptido tetramérico presenta actividad contra los aislados clínicos evaluados, con Concentraciones Mínimas Inhibitorias (CMI) en el rango de 11 μM a 22 μM para bacterias Gram positivas y 5 μM a 22 μM para Gram negativas; estos resultados muestran que este péptido LfcinB (20-25)4 con actividad antibacteriana, tanto en cepas de referencia como en aislados clínicos, es una alternativa viable para el desarrollo de nuevos agentes terapéuticos. (Texto tomado de la fuente)Antimicrobial peptides (PAMs) are an alternative to the development of new antibacterial therapies, which could counteract the ascending number of antibiotic- resistant microorganisms that have increased the global public health problem. In the latest WHO reports in 2018, it indicates that bacteria such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus, exhibit resistance against first-line antibiotics and are classified as resistant and multidrug-resistant strains, demonstrating the inefficiency of drugs worldwide. Within this context, peptides derived from Lactoferricin Bovina (LfcinB) containing the minimum motif, have been evaluated against Gram-positive and Gram-negative reference strains. In this work, the tetrameric peptide LfcinB (20- 25)4 was evaluated against clinical isolates of S. aureus and E. coli that have been classified as multidrug-resistant by the Institute of Cancerology of Bogota, with a new identification through MALDI TOF. The activity of this peptide was demonstrated against the clinical isolates evaluated, having a minimal inhibitory concentration (MIC) within the range of 11 – 22μM for Gram-positive bacteria and 5 – 22μM for Gram negatives. In addition, the activity in combination with ciprofloxacin was evaluated for one of the isolates with higher percentages of antibiotic resistance, resulting in an additive effect that maintained the concentration of the peptide. All these results show that the tetrameric peptide LfcinB (20-25)4 with antibacterial activity, is a viable alternative for the development of new therapeutic agents. (Text taken from source)MaestríaMagíster en Ciencias - MicrobiologíaMicrobiología93 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - MicrobiologíaInstituto de Biotecnología (IBUN)Facultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::615 - Farmacología y terapéuticaAntibacterianosAnti-Bacterial AgentsEnfermedades transmisiblesCommunicable DiseasesLactoferricina BovinaActividad antibacterianaAislados clínicosMultirresistentesPéptidos antimicrobianosBovine lactoferricinAntibacterial activityClinical isolatesAntimicrobial peptidesActividad antibacteriana del péptido LfcinB (20-25)4 contra aislados clínicos multirresistentes de E. coli Y S. aureusAntibacterial activity of the LfcinB (20-25) 4 peptide against multi-resistant clinical isolates of E. coli and S. aureusTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMInoue H, Minghui R. Antimicrobial resistance: Translating political commitment into national action. Bull World Health Organ. 2017;95(4):242- 242A.Shrivastava SR, Shrivastava PS, Ramasamy J. World health organization releases global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. JMS - J Med Soc. 2018;32(1):76–7.Exner M, Bhattacharya S, Christiansen B, Gebel J, Goroncy-Bermes P, Hartemann P, et al. Antibiotic resistance: What is so special about multidrug- resistant Gram-negative bacteria? GMS Hyg Infect Control [Internet]. 2017;12:Doc05. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28451516%0Ahttp://www.pubmedce ntral.nih.gov/articlerender.fcgi?artid=PMC5388835Willyard C. The drug-resistant bacteria that pose the greatest health threats. Nature. 2017;543(7643):15.Aminov RI. A brief history of the antibiotic era: Lessons learned and challenges for the future. Front Microbiol. 2010;1(DEC):1–7.Blair JMA, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJV. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol [Internet]. 2015;13(1):42–51. Available from: http://dx.doi.org/10.1038/nrmicro3380OMS. Resistencia a los antimicrobianos Situación actual Resistencia de las bacterias [Internet]. 2020. Available from: https://www.who.int/es/news- room/fact-sheets/detail/resistencia-a-los-antimicrobianosGrupo de Microbiología Subdirección Laboratorio Nacional de Referencia (SLNR). Infecciones asociadas a la atención en salud. Epidemiología de las infecciones asociadas a la atención en salud. 2019.Ministerio de Salud y Protección Social. Plan Nacional de Respuesta a la Resistencia a los Antimicrobianos - plan estratégico. 2018;66. Available from: https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/MET /plan-respuesta-resistencia-antimicrobianos.pdfMaldonado NA, Múnera MI, López JA, Sierra P, Robledo C, Robledo J, et al. Tendencias de la resistencia a antibióticos en Medellín y en los municipios del área metropolitana entre 2007 y 2012: Resultados de seis años de vigilancia. Biomedica. 2014;34(3):433–46.Chung PY, Khanum R. Antimicrobial peptides as potential anti-biofilm agents against multidrug-resistant bacteria. J Microbiol Immunol Infect [Internet]. 2017;50(4):405–10. Available from: http://dx.doi.org/10.1016/j.jmii.2016.12.005Bahar AA, Ren D. Antimicrobial peptides. Pharmaceuticals. 2013;6(12):1543– 75.Rodríguez-Franco DA, Vázquez-Moreno L, Ramos-Clamont Montfort G. Actividad antimicrobiana de la lactoferrina: Mecanismos y aplicaciones clínicas potenciales. Rev Latinoam Microbiol. 2005;47(3–4):102–11.Murata M, Wakabayashi H, Yamauchi K, Abe F. Identification of milk proteins enhancing the antimicrobial activity of lactoferrin and lactoferricin. J Dairy Sci [Internet]. 2013;96(8):4891–8. Available from: http://dx.doi.org/10.3168/jds.2013-6612L.Cheng-Foh FM, S.Shamala. Intracellular Targeting Mechanisms by antimicrobial peptides. 2017;61(4):1–16.Yamauchi K, Tomita M, Giehl TJ, Ellison RT. Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment. Infect Immun.1993;61(2):719–28.Vorland LH, Ulvatne H, Andersen J, Haukland HH, Rekdal Ø, Svendsen JS, et al. Lactoferricin of bovine origin is more active than lactoferricins of human, murine and caprine origin. Scand J Infect Dis. 1998;30(5):513–7.Sinha M, Kaushik S, Kaur P, Sharma S, Singh TP. Antimicrobial lactoferrin peptides: The hidden players in the protective function of a multifunctional protein. Int J Pept. 2013;2013(February 2015).Schibli DJ, Hwang PM, Vogel HJ. The structure of the antimicrobial active center of lactoferricin B bound to sodium dodecyl sulfate micelles. FEBS Lett. 1999;446(2–3):213–7.León-Calvijo MA, Leal-Castro AL, Almanzar-Reina GA, Rosas-Pérez JE, García-Castañeda JE, Rivera-Monroy ZJ. Antibacterial Activity of Synthetic Peptides Derived from Lactoferricin against Escherichia coli ATCC 25922 and Enterococcus faecalis ATCC 29212. Biomed Res Int. 2015 Mar;2015:1–8.Huertas N de J, Monroy ZJR, Medina RF, Castañeda JEG. Antimicrobial Activity of Truncated and Polyvalent Peptides Derived from the FKCRRQWQWRMKKGLA Sequence against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. Molecules. 2017;22(6).Vargas Casanova Y, Rodríguez Guerra JA, Umaña Pérez YA, Leal Castro AL, Almanzar Reina G, García Castañeda JE, et al. Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB- 468 and MDA-MB-231 Breast Cancer Cell Lines. Molecules. 2017;22(10):1–11.Vargas-Casanova Y, Rodríguez-Mayor AV, Cardenas KJ, Leal-Castro AL, Muñoz-Molina LC, Fierro-Medina R, et al. Synergistic bactericide and antibiotic effects of dimeric, tetrameric, or palindromic peptides containing the RWQWR motif against Gram-positive and Gram-negative strains. RSC Adv. 2019;9(13):7239–45.Alby K, Miller MB. Mechanisms and Detection of Antimicrobial Resistance [Internet]. Fifth Edit. Principles and Practice of Pediatric Infectious Diseases. Elsevier Inc.; 2017. 1467-1478.e4 p. Available from: http://dx.doi.org/10.1016/B978-0-323-40181-4.00290-5Theuretzbacher U. Global antibacterial resistance: The never-ending story. J Glob Antimicrob Resist [Internet]. 2013;1(2):63–9. Available from: http://dx.doi.org/10.1016/j.jgar.2013.03.010Gómez Rubio A. Consumo de antibióticos en el ámbito hospitalario en Colombia, primer semestre de 2019. Inst Nac Salud. 2019;1–16.Afacan NJ, Yeung ATY, Pena OM, Hancock REW. Therapeutic potential of host defense peptides in antibiotic-resistant infections. Curr Pharm Des [Internet]. 2012;18(6):807–19. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22236127Germán Alberto Téllez1, Jhon Carlos Castaño1. Péptidos antimicrobianos Antimicrobial peptides. 2010;14(1):55–67. Available from: www.ncbi.nlm.nih.gov/pubmedRana M, Chatterjee S, Kochhar S, Pereira BMJ. Antimicrobial Peptides: a New Dawn for Regulating Fertility and Reproductive Tract Infections. J Endocrinol Reprod [Internet]. 2006;2:88–95. Available from: http://srbce.org/journal12b/002.pdfBellamy W, Takase M, Wakabayashi H, Kawase K, Tomita M. Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N‐terminal region of bovine lactoferrin. J Appl Bacteriol. 1992;73(6):472–9.Schiffer M, Chang CH, Stevens FJ. The functions of tryptophan residues in membrane proteins. Protein Eng Des Sel. 1992;5(3):213–4.De Jesus AJ, Allen TW. The role of tryptophan side chains in membrane protein anchoring and hydrophobic mismatch. Biochim Biophys Acta - Biomembr [Internet]. 2013;1828(2):864–76. Available from: http://dx.doi.org/10.1016/j.bbamem.2012.09.009Vorland LH, Osbakk SA, Perstølen T, Ulvatne H, Rekdal Ø, Svendsen JS, et al. Interference of the antimicrobial peptide lactoferricin B with the action of various antibiotics against Escherichia coli and Staphylococcus aureus. Scand J Infect Dis. 1999;31(2):173–7.Feng X jun, Wang J hua, Shan A shan, Teng D, Yang Y lin, Yao Y, et al. Fusion expression of bovine lactoferricin in Escherichia coli. Protein Expr Purif. 2006;47(1):110–7.Vargas Casanova Y. Evaluación De La Actividad Antibacteriana De Péptidos Diméricos Y Tetraméricos Derivados De Lactoferricina Bovina Contra Bacterias Gram Positivas Y Gram Negativas. Universidad Nacional de Colombia; 2018.Huertas Méndez NDJ, Vargas Casanova Y, Gómez Chimbi AK, Hernández E, Leal Castro AL, Melo Diaz JM, et al. Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Antimicrobial Activity against E. coli ATCC 11775, S. maltophilia ATCC 13636 and S. enteritidis ATCC 13076. Molecules. 2017;22(3):1–10.Sinha M, Kaushik S, Kaur P, Sharma S, Singh TP. Antimicrobial lactoferrin peptides: The hidden players in the protective function of a multifunctional protein. Int J Pept. 2013;2013.Gifford JL, Hunter HN, Vogel HJ. Lactoferricin: A lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties. CellMol Life Sci. 2005;62(22):2588–98.Ptaszyńska N, Olkiewicz K, Okońska J, Gucwa K, Łęgowska A, Gitlin-Domagalska A, et al. Peptide conjugates of lactoferricin analogues and antimicrobials—Design, chemical synthesis, and evaluation of antimicrobial activity and mammalian cytotoxicity. Peptides [Internet]. 2019;117(March):170079. Available from: https://doi.org/10.1016/j.peptides.2019.04.006Farnaud S, Spiller C, Moriarty LC, Patel A, Gant V, Odell EW, et al. Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity. FEMS Microbiol Lett. 2004;233(2):193–9.Vega SC, Martínez DA, Chalá M del S, Vargas HA, Rosas JE. Design, synthesis and evaluation of branched RRWQWR-based peptides as antibacterial agents against clinically relevant gram-positive and gram-negative pathogens. Front Microbiol. 2018;9(MAR).Vega Chaparro SC, Valencia Salguero JT, Martínez Baquero DA, Rosas Pérez JE. Effect of Polyvalence on the Antibacterial Activity of a Synthetic Peptide Derived from Bovine Lactoferricin against Healthcare-Associated Infectious Pathogens. Biomed Res Int. 2018;2018.Concepción Porrero Calonge. Detección y caracterización de Staphylococcus aureus procedentes de aninales y aguas. Universidad Complutense de Madrid; 2014.Borraz Ordás C. Epidemiología De La Resistencia a Meticilina [Internet].Universidad de barcelona; 2003. Available from: http://www.tdx.cat/bitstream/handle/10803/2513/CBO_TESIS_DOCTORAL.pdfDavies J, Davies D. Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev. 2010;74(3):417–33.Leal-Castro AL, Álvarez CA. Resultados de la vigilancia de la resistencia bacteriana. 2019.Lacueva Arnedo M. Resistencia a antibióticos en Staphylococcus aureus. Evolución y perspectiva actual [Internet]. Universidad complutense; 2017. Available from: https://eprints.ucm.es/54765/Zhang HZ, Hackbarth CJ, Chansky KM, Chambers HF. A proteolytic transmembrane signaling pathway and resistance to β-lactams in staphylococci. Science (80- ). 2001;291(5510):1962–5.Shajari G, Khorshidi A, Moosavi G. Vancomycin resistance in Staphylococcus aureus strains. Arch Razi Inst. 2017;90(54):107–10.Araos R, García P, Chanqueo L, Labarca J. Daptomycin: Pharmacological characteristics and its role in the treatment of gram positive infections. Rev Chil Infectología. 2012;29(2):127–31.Casanova, Natalia Gómez, María, Siller Ruiz JLMB. Mechanisms of resistance to Daptomycin in Staphylococcus aureus. Kasmera [Internet]. 2010;38(6):36–44. Available from: http://seq.es/wp- content/uploads/2017/12/gomez25oct2017.pdfVelasco C de caceres. Evolución de la resistencia a antibióticos en Staphylococcus aureus . Universidad Complutense; 2016.Ruiz Larrea F, Lantero M, Torres Gómez C, Portillo A, Zarazaga Chamorro M, Olarte I, et al. Resistencia a antibióticos macrólidos-lincosamidas- estreptograminas y mecanismos implicados en cepas clínicas de “Streptococcus” spp. en La Rioja. Zubía. 2000;12(12):11–26.McCallum N, Berger-Bächi B, Senn MM. Regulation of antibiotic resistance in Staphylococcus aureus. Int J Med Microbiol. 2010;300(2–3):118–29.Benito Pascual D. Líneas genéticas, virulencia y resistencia a antibióticos en Staphylococcus aureus de diferentes orígenes. Análisis de marcadores de adaptación al huésped y comportamiento en Caenorhabditis elegans. Universidad de la Rioja; 2015.Truong-Bolduc QC, Dunman PM, Strahilevitz J, Projan SJ, Hooper DC. MgrA is a multiple regulator of two new efflux pumps in Staphylococcus aureus. J Bacteriol. 2005;187(7):2395–405.Romeu B. Caracterización de cepas de Escherichia coli de importancia clínica humana aisladas de ecosistemas dulceacuícolas de La Habana. Repositorio de Tesis Universidad de La Habana. 2012.Grupo de evaluación de riesgos de inocuidad de Alimentos. Perfil de riesgo de Escherichia coli enterotoxigénica y verotoxigénica en queso fresco [Internet]. Instituto Nacional de Salud. 2015. Available from: http://www.ghbook.ir/index.php?name option=com_dbook&task=readonline&book_id=13650&page=73&chkha&نوین shk=ED9C9491B4&Itemid=218&lang=fa&tmpl=componentAlonso CA. Epidemiología molecular en Escherichia coli procedente de fauna salvaje : resistencia antimicrobiana , virulencia y diversidad y diversidad genética. Universidad de la Rioja; 2018.Vargas CRS. Elaboración y evaluación del material didáctico variedades enterovirulentas de Escherichia coli [Internet]. UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO; 2014. Available from: https://www.zaragoza.unam.mx/portal/wp- content/Portal2015/Licenciaturas/qfb/tesis/tesis_salas_vargas.pdfGales AC, Castanheira M, Jones RN, Sader HS. Antimicrobial resistance among Gram-negative bacilli isolated from Latin America: Results from SENTRY Antimicrobial Surveillance Program (Latin America, 2008-2010). Diagn Microbiol Infect Dis [Internet]. 2012;73(4):354–60. Available from: http://dx.doi.org/10.1016/j.diagmicrobio.2012.04.007García-Hernández AM, García-Vázquez E, Hernández-Torres A, Ruiz J, Yagüe G, Herrero JA, et al. Bacteraemia due to Escherichia coli producing extended-spectrum beta-lactamases (ESBL): clinical relevance and today’s insights. Rev Esp Quimioter [Internet]. 2011;24(2):57–66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21666996Rice LB. Mechanisms of resistance and clinical relevance of resistance to β- lactams, glycopeptides, and fluoroquinolones. Mayo Clin Proc [Internet]. 2012;87(2):198–208. Available from: http://dx.doi.org/10.1016/j.mayocp.2011.12.003Serra A. QUINOLONAS. Separata. 2008;16.Munita JM, Arias CA. Mechanisms of Antibiotic Resistance. Annu Rep Med Chem. 2016;4(2):119–27.Grünbaum F. Resistencia a aminoglucósidos en ENTEROBACTERIACEAE [Internet]. Universidad autónoma de Barcelona; 2011. Available from: http://www.tdx.cat/bitstream/handle/10803/42291/fg1de1.pdf?sequence=1Maldonado N, Robledo C, Robledo J. La espectrometría de masas MALDI-TOF en el laboratorio de microbiología clínica. Infectio. 2018;22(1):35–45.Demirev P, Sandrin T. Aplications of mass spectrometry in microbiology. New York: Springer Cham Heidelberg; 2016. 1–336 p.Sampedro A, Ceballos Mendiola J, Aliaga Martínez L. MALDI-TOF Commercial Platforms for Bacterial Identification [Internet]. The Use of Mass Spectrometry Technology (MALDI-TOF) in Clinical Microbiology. Elsevier Inc.; 2018. 47–57 p. Available from: http://dx.doi.org/10.1016/B978-0-12- 814451-0.00003-4Cramer R. Advances in MALDI and laser-induced soft ionization mass spectrometry. Adv MALDI Laser-Induced Soft Ioniz Mass Spectrom. 2015;1– 286.CLSI. M100 Performance Standards for Antimicrobial Susceptibility Testing [Internet]. Vol. 8, Journal of Services Marketing. 2019. 27–39 p. Available from: http://www.emeraldinsight.com/doi/10.1108/08876049410065598Wiegand I, Hilpert K, Hancock REW. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc. 2008;3(2):163–75.Doern CD. When does 2 plus 2 equal 5? A review of antimicrobial synergy testing. J Clin Microbiol. 2014;52(12):4124–8.Vargas-Casanova Y. EVALUACIÓN DE LA ACTIVIDAD ANTIBACTERIANA DE PÉPTIDOS DIMÉRICOS Y TETRAMÉRICOS DERIVADOS DE LACTOFERRICINA BOVINA CONTRA BACTERIAS GRAM POSITIVAS Y GRAM NEGATIVAS. Universidad nacional de Colombia; 2018.Toledo MRF, Trabulsi LR. Correlation between biochemical and serological characteristics of Escherichia coli and results of the Sereny test. J Clin Microbiol. 1983;17(3):419–21.Park JJ, Seo Y Bin, Lee J. Antimicrobial susceptibilities of Enterobacteriaceae in community-acquired urinary tract infections during a 5-year period: A single hospital study in Korea. Infect Chemother. 2017;49(3):184–93.Ceballos-Garzón A, Cabrera E, Cortes-Fraile GC, León A, Aguirre-Guataqui K, Linares-Linares MY, et al. In-house protocol and performance of MALDI- TOF MS in the early diagnosis of bloodstream infections in a fourth-level hospital in Colombia: Jumping to full use of this technology. Int J Infect Dis. 2020;101:85–9.Bhat G, Bhat G. Atypical Escherichia Coli in Urinary Tract Infection. Trop Doct. 1995;25(3):127.Raksha R, Srinivasa H, Macaden RS. Occurrence and characterisation of Uropathogenic Escherichia coli in urinary tract infections. Indian J Med Microbiol [Internet]. 2003;21(2):102–7. Available from: https://doi.org/10.1016/S0255-0857(21)03130-3T. R, M J. Prevalence of Atypical E . coli Causing Urinary Tract Infection in a Tertiary Care Hospital . Australas Med J. 2010;3(8):545–6.Bajpai T, Pandey M, Varma M, Bhatambare G. Importance of identification of lactose nonfermenting Escherichia coli and their prevalence in urinary isolates. CHRISMED J Heal Res. 2016;3(4):288.Kaczmarek A, Skowron K, Budzyńska A, Grudlewska K, Gospodarek- Komkowska E. Virulence genes and antimicrobial susceptibility of lactose- negative and lactose-positive strains of Escherichia coli isolated from pregnant women and neonates. Folia Microbiol (Praha). 2017;62(5):363–71.Chang J, Yu J, Lee H, Ryu H, Park K, Park YJ. Prevalence and characteristics of lactose non-fermenting Escherichia coli in urinary isolates. J Infect Chemother [Internet]. 2014;20(11):738–40. Available from: http://dx.doi.org/10.1016/j.jiac.2014.07.005Hrabák J, Chudác ̌ková E, Walková R. Matrix-assisted laser desorption ionization-time of flight (MALDITOF) mass spectrometry for detection of antibiotic resistance mechanisms: From research to routine diagnosis. Clin Microbiol Rev. 2013;26(1):103–14.Ceballos-Garzon A, Amado D, Vélez N, Jiménez-A MJ, Rodríguez C, Parra- Giraldo CM. Development and validation of an in-house library of colombian candida auris strains with maldi-TOF MS to improve yeast identification. J Fungi. 2020;6(2):1–8.Sanguinetti M, Posteraro B. Mass spectrometry applications in microbiology beyond microbe identification: progress and potential. Expert Rev Proteomics. 2016;13(10):965–77.Kallow W, Erhard M, Shah H, Raptakis E, Welker M. MALDI - TOF MS for Microbial Identifi cation : Years of Experimental Development to an. In: Shah H, Gharbia S, editors. Mass Spectrometry for Microbial Proteomics. London; 2010. p. 255–76. 88. Dingle TC, Butler-Wu SM. MALDI-TOF mass spectrometry for microorganism identification. Clin Lab Med. 2013;33(3):589–609.Gil Gonzalo A. Espectrometría MALDI‐TOF aplicada a levaduras enológicas: identificación. [Internet]. Universidad de Valladolid; 2014. Available from: http://uvadoc.uva.es/bitstream/handle/10324/38124/TFG- G3567.pdf?sequence=1.Cipolla L, Rocca F, Armitano RI, Martinez C, Almuzara M, Faccone D, et al. Development and evaluation of an in-house database for quick identification of Burkholderia contaminans by MALDI-TOF MS. Rev Argent Microbiol [Internet]. 2019;51(3):255–8. Available from: https://doi.org/10.1016/j.ram.2018.09.001Bou G, Fernández-Olmos A, García C, Sáez-Nieto JA, Valdezate S. Métodos de identificación bacteriana en el laboratorio de microbiología. Enferm Infecc Microbiol Clin. 2011;29(8):601–8.León-Calvijo MA, Leal-Castro AL, Almanzar-Reina GA, Rosas-Pérez JE, García-Castañeda JE, Rivera-Monroy ZJ. Antibacterial Activity of Synthetic Peptides Derived from Lactoferricin against Escherichia coli ATCC 25922 and Enterococcus faecalis ATCC 29212 . Biomed Res Int. 2015;2015:1–8.Flores-Villaseñor H, Canizalez-Román A, Reyes-Lopez M, Nazmi K, De La Garza M, Zazueta-Beltrán J, et al. Bactericidal effect of bovine lactoferrin, LFcin, LFampin and LFchimera on antibiotic-resistant Staphylococcus aureus and Escherichia coli. BioMetals. 2010;23(3):569–78.Pane K, Durante L, Crescenzi O, Cafaro V, Pizzo E, Varcamonti M, et al. Antimicrobial potency of cationic antimicrobial peptides can be predicted from their amino acid composition: Application to the detection of “cryptic” antimicrobial peptides. J Theor Biol [Internet]. 2017;419(January):254–65. Available from: http://dx.doi.org/10.1016/j.jtbi.2017.02.012Yau WM, Wimley WC, Gawrisch K, White SH. The preference of tryptophan for membrane interfaces. Biochemistry. 1998;37(42):14713–8.Sun H, Greathouse D V., Andersen OS, Koeppe RE. The preference of tryptophan for membrane interfaces: Insights from N-methylation of tryptophans in gramicidin channels. J Biol Chem. 2008;283(32):22233–43.Wimley WC, White SH. Membrane Partitioning: Distinguishing Bilayer Effects from the Hydrophobic Effect. Biochemistry. 1993;32(25):6307–12.Chan DI, Prenner EJ, Vogel HJ. Tryptophan- and arginine-rich antimicrobial peptides: Structures and mechanisms of action. Biochim Biophys Acta - Biomembr. 2006;1758(9):1184–202.Haukland HH, Ulvatne H, Sandvik K, Vorland LH. The antimicrobial peptides lactoferricin B and magainin 2 cross over the bacterial cytoplasmic membrane and reside in the cytoplasm. FEBS Lett. 2001;508(3):389–93.Vergis J, Malik SS, Pathak R, Kumar M, Ramanjaneya S, Kurkure NV, et al. Exploiting Lactoferricin (17–30) as a Potential Antimicrobial and Antibiofilm Candidate Against Multi-Drug-Resistant Enteroaggregative Escherichia coli. Front Microbiol. 2020;11(September):1–13.Bonapace CR, Bosso JA, Friedrich L V., White RL. Comparison of methods of interpretation of checkerboard synergy testing. Diagn Microbiol Infect Dis. 2002;44(4):363–6.EspecializadaDiseño y obtención de nuevos agentes antibacterianos basados en dendrímero péptido – resorcinareno: Una alternativa para combatir la resistencia bacteriana.MINCIENCIAS (COLCIENCIAS)LICENSElicense.txtlicense.txttext/plain; charset=utf-83964https://repositorio.unal.edu.co/bitstream/unal/79982/1/license.txtcccfe52f796b7c63423298c2d3365fc6MD51ORIGINAL1032464031.2021.pdf1032464031.2021.pdfTesis de Maestría en Ciencias - Microbiologíaapplication/pdf1720308https://repositorio.unal.edu.co/bitstream/unal/79982/2/1032464031.2021.pdfcdf97231b0f273e3bca22c9be1ea79d0MD52THUMBNAIL1032464031.2021.pdf.jpg1032464031.2021.pdf.jpgGenerated Thumbnailimage/jpeg4801https://repositorio.unal.edu.co/bitstream/unal/79982/3/1032464031.2021.pdf.jpge24c49e7db344b8bf07e0e2b64c296beMD53unal/79982oai:repositorio.unal.edu.co:unal/799822024-07-28 01:11:59.646Repositorio Institucional Universidad Nacional de Colombiarepositorio_nal@unal.edu.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 |