Caracterización de factores inmunológicos y microbiológicos asociados a la colonización e infección por Staphylococcus aureus

Staphylococcus aureus (S. aureus) es un colonizador y patógeno humano eficaz. Sin embargo, los mecanismos moleculares e inmunológicos involucrados en la interacción de S. aureus con el hospedero durante la colonización y la infección no se conocen por completo. No obstante, esto requiere una compren...

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Autores:: Montes Guevara, Oscar Alonso

Tipo de recurso:: Doctoral thesis

Fecha de publicación:: 2023

Institución:: Universidad de Cartagena

Repositorio:: Repositorio Universidad de Cartagena

Idioma:: spa

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dc.title.spa.fl_str_mv	Caracterización de factores inmunológicos y microbiológicos asociados a la colonización e infección por Staphylococcus aureus
title	Caracterización de factores inmunológicos y microbiológicos asociados a la colonización e infección por Staphylococcus aureus
spellingShingle	Caracterización de factores inmunológicos y microbiológicos asociados a la colonización e infección por Staphylococcus aureus Inmunología Inmunología molecular Descontaminación biológica Estafilococos
title_short	Caracterización de factores inmunológicos y microbiológicos asociados a la colonización e infección por Staphylococcus aureus
title_full	Caracterización de factores inmunológicos y microbiológicos asociados a la colonización e infección por Staphylococcus aureus
title_fullStr	Caracterización de factores inmunológicos y microbiológicos asociados a la colonización e infección por Staphylococcus aureus
title_full_unstemmed	Caracterización de factores inmunológicos y microbiológicos asociados a la colonización e infección por Staphylococcus aureus
title_sort	Caracterización de factores inmunológicos y microbiológicos asociados a la colonización e infección por Staphylococcus aureus
dc.creator.fl_str_mv	Montes Guevara, Oscar Alonso
dc.contributor.advisor.none.fl_str_mv	Reyes Ramos, Niradiz
dc.contributor.author.none.fl_str_mv	Montes Guevara, Oscar Alonso
dc.subject.armarc.none.fl_str_mv	Inmunología Inmunología molecular Descontaminación biológica Estafilococos
topic	Inmunología Inmunología molecular Descontaminación biológica Estafilococos
description	Staphylococcus aureus (S. aureus) es un colonizador y patógeno humano eficaz. Sin embargo, los mecanismos moleculares e inmunológicos involucrados en la interacción de S. aureus con el hospedero durante la colonización y la infección no se conocen por completo. No obstante, esto requiere una comprensión adecuada de los determinantes involucrados en la colonización e infección de su hospedero. Esta tesis tuvo como objetivo central realizar la caracterización de varios factores inmunológicos y microbiológicos que han sido previamente asociados a la colonización e infección por S. aureus, en una población de pacientes con diagnóstico confirmado de infección por esta bacteria e individuos controles sanos de la ciudad de Cartagena de Indias y áreas geográficas circunvecinas. Parte de los resultados derivados de este trabajo han sido publicados en tres artículos en revistas indexadas internacionalmente. En el artículo 1 (publicado), el análisis del microbioma nasal de individuos sanos reveló que la diversidad bacteriana y fúngica es más abundante en las personas colonizadas por S. aureus que en los no portadores, asimismo se corroboró que muchas especies micóticas están conviviendo dentro del vestíbulo nasal sano en una biomasa y riqueza sustanciales. En el artículo 2 (publicado), se detalla la primera representación de la distribución poblacional de SARM y SASM responsables de infecciones atendidas en el hospital pediátrico participante, donde se identificaron los clones epidémicos más prevalentes en la población en estudio, ST8-SARM-IVc, ST923-SARM-IVa y ST8-SARM-IVa. En el artículo 3 (manuscrito en preparación), en pacientes con celulitis comparados con portadores y no-portadores sanos de S. aureus, se detectaron niveles séricos de tres quimiocinas proinflamatorias, IL-8, RANTES, y MDC, significativamente elevadas en estos pacientes. Estos hallazgos aportan información nueva sobre la participación potencial de algunas quimiocinas proinflamatorias en los procesos de colonización e infección por S. aureus. En el artículo 4 (manuscrito en preparación), la producción de biopelículas por aislados clínicos SARM y SASM fue significativamente mayor en comparación con la producida por aislamientos colonizantes. El análisis de la relación entre la capacidad de formación de biopelículas y el perfil de varios genes previamente asociados al proceso de producción de biopelículas, permitió detectar diferencias significativas entre los dos grupos de aislamientos, encontrándose una mayor frecuencia del gen ica A en el grupo de aislamientos clínicos. En el artículo 5 (publicado), en el análisis del genoma secuenciado del aislamiento COL52-A5 obtenido de un individuo sano colonizado persistentemente, se encontró numerosos factores de virulencia y resistencia. El esclarecimiento de cuáles son las características genómicas de esta bacteria que favorecen el transporte persistente en individuos sanos requiere que se realice un análisis comparativo detallado de los genomas secuenciados de un número adecuado de cepas persistentes e intermitentes. En el artículo 6 (manuscrito en preparación), las evidencias de este trabajo sugieren que HLADRB1*07:01:01 pudiera estar implicado en la susceptibilidad al transporte nasal de S. aureus en individuos sanos colonizados con esta bacteria. Se requieren estudios adicionales con un tamaño muestral mayor para verificar los hallazgos encontrados. En consecuencia, los resultados alcanzados en la elaboración de esta tesis destacan las complejidades de los mecanismos involucrados en la interacción de la bacteria S. aureus con el hospedero humano. Se requieren estudios adicionales para lograr un mayor esclarecimiento de los factores involucrados en los procesos de colonización e infección llevados a cabo por esta bacteria en las poblaciones humanas.
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dc.date.accessioned.none.fl_str_mv	2023-02-15T14:56:29Z
dc.date.available.none.fl_str_mv	2023-02-15T14:56:29Z
dc.date.issued.none.fl_str_mv	2023
dc.type.spa.fl_str_mv	Trabajo de grado - Doctorado
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dc.rights.spa.fl_str_mv	Derechos Reservados - Universidad de Cartagena, 2023
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spelling	Reyes Ramos, NiradizMontes Guevara, Oscar Alonso2023-02-15T14:56:29Z2023-02-15T14:56:29Z2023https://hdl.handle.net/11227/15960http://dx.doi.org/10.57799/11227/96Staphylococcus aureus (S. aureus) es un colonizador y patógeno humano eficaz. Sin embargo, los mecanismos moleculares e inmunológicos involucrados en la interacción de S. aureus con el hospedero durante la colonización y la infección no se conocen por completo. No obstante, esto requiere una comprensión adecuada de los determinantes involucrados en la colonización e infección de su hospedero. Esta tesis tuvo como objetivo central realizar la caracterización de varios factores inmunológicos y microbiológicos que han sido previamente asociados a la colonización e infección por S. aureus, en una población de pacientes con diagnóstico confirmado de infección por esta bacteria e individuos controles sanos de la ciudad de Cartagena de Indias y áreas geográficas circunvecinas. Parte de los resultados derivados de este trabajo han sido publicados en tres artículos en revistas indexadas internacionalmente. En el artículo 1 (publicado), el análisis del microbioma nasal de individuos sanos reveló que la diversidad bacteriana y fúngica es más abundante en las personas colonizadas por S. aureus que en los no portadores, asimismo se corroboró que muchas especies micóticas están conviviendo dentro del vestíbulo nasal sano en una biomasa y riqueza sustanciales. En el artículo 2 (publicado), se detalla la primera representación de la distribución poblacional de SARM y SASM responsables de infecciones atendidas en el hospital pediátrico participante, donde se identificaron los clones epidémicos más prevalentes en la población en estudio, ST8-SARM-IVc, ST923-SARM-IVa y ST8-SARM-IVa. En el artículo 3 (manuscrito en preparación), en pacientes con celulitis comparados con portadores y no-portadores sanos de S. aureus, se detectaron niveles séricos de tres quimiocinas proinflamatorias, IL-8, RANTES, y MDC, significativamente elevadas en estos pacientes. Estos hallazgos aportan información nueva sobre la participación potencial de algunas quimiocinas proinflamatorias en los procesos de colonización e infección por S. aureus. En el artículo 4 (manuscrito en preparación), la producción de biopelículas por aislados clínicos SARM y SASM fue significativamente mayor en comparación con la producida por aislamientos colonizantes. El análisis de la relación entre la capacidad de formación de biopelículas y el perfil de varios genes previamente asociados al proceso de producción de biopelículas, permitió detectar diferencias significativas entre los dos grupos de aislamientos, encontrándose una mayor frecuencia del gen ica A en el grupo de aislamientos clínicos. En el artículo 5 (publicado), en el análisis del genoma secuenciado del aislamiento COL52-A5 obtenido de un individuo sano colonizado persistentemente, se encontró numerosos factores de virulencia y resistencia. El esclarecimiento de cuáles son las características genómicas de esta bacteria que favorecen el transporte persistente en individuos sanos requiere que se realice un análisis comparativo detallado de los genomas secuenciados de un número adecuado de cepas persistentes e intermitentes. En el artículo 6 (manuscrito en preparación), las evidencias de este trabajo sugieren que HLADRB1*07:01:01 pudiera estar implicado en la susceptibilidad al transporte nasal de S. aureus en individuos sanos colonizados con esta bacteria. Se requieren estudios adicionales con un tamaño muestral mayor para verificar los hallazgos encontrados. En consecuencia, los resultados alcanzados en la elaboración de esta tesis destacan las complejidades de los mecanismos involucrados en la interacción de la bacteria S. aureus con el hospedero humano. Se requieren estudios adicionales para lograr un mayor esclarecimiento de los factores involucrados en los procesos de colonización e infección llevados a cabo por esta bacteria en las poblaciones humanas.DoctoradoDoctor(a) en Ciencias Biomédicasapplication/pdfspaUniversidad de CartagenaFacultad de MedicinaCartagena de IndiasDoctorado en Ciencias BiomédicasDerechos Reservados - Universidad de Cartagena, 2023https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial 4.0 Internacional (CC BY-NC 4.0)http://purl.org/coar/access_right/c_abf2Caracterización de factores inmunológicos y microbiológicos asociados a la colonización e infección por Staphylococcus aureusTrabajo de grado - Doctoradoinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_db06Textinfo:eu-repo/semantics/doctoralThesishttps://purl.org/redcol/resource_type/TDhttp://purl.org/coar/version/c_970fb48d4fbd8a85InmunologíaInmunología molecularDescontaminación biológicaEstafilococosCervantes-García E, García-González R, Salazar-Schettino PM. Características generales del Staphylococcus aureus. Revista Mexicana de Patología Clínica y Medicina de Laboratorio. 2014;61(1):28-40.de Souza Lemos A, de Souza ACMF, Karas B, Calixto CM, Meijerink CI, Nascimento FC, et al. Prevalence of Staphylococcus aureus and MRSA among Medical students: a literature review. Research, Society and Development. 2021;10(11):e347101119536-eKoneman EW, Allen SD, Janda W, Schreckenberger P, Winn W. Diagnostic microbiology. The nonfermentative gram-negative bacilli Philedelphia: Lippincott-Raven Publishers. 1997:253-320.Kuroda M, Ohta T, Uchiyama I, Baba T, Yuzawa H, Kobayashi I, et al. Whole genome sequencing of meticillin-resistant Staphylococcus aureus. The Lancet. 2001;357(9264):1225-40Liu L, Wang Y, Bojer MS, Andersen PS, Ingmer H. High persister cell formation by clinical Staphylococcus aureus strains belonging to clonal complex 30. Microbiology. 2020;166(7):654-8.van Belkum A. Staphylococcal colonization and infection: homeostasis versus disbalance of human (innate) immunity and bacterial virulence. Current opinion in infectious diseases. 2006;19(4):339-44van Belkum A. Staphylococcal colonization and infection: homeostasis versus disbalance of human (innate) immunity and bacterial virulence. Current opinion in infectious diseases. 2006;19(4):339-44Sakr A, Bregeon F, Mege JL, Rolain JM, Blin O. Staphylococcus aureus Nasal Colonization: An Update on Mechanisms, Epidemiology, Risk Factors, and Subsequent Infections. Front Microbiol. 2018;9:2419.Mulcahy ME, McLoughlin RM. Host-Bacterial Crosstalk Determines Staphylococcus aureus Nasal Colonization. Trends Microbiol. 2016;24(11):872-86.Modak R, Das Mitra S, Vasudevan M, Krishnamoorthy P, Kumar M, Bhat AV, et al. Epigenetic response in mice mastitis: Role of histone H3 acetylation and microRNA(s) in the regulation of host inflammatory gene expression during Staphylococcus aureus infection. Clin Epigenetics. 2014;6(1):12.Liu Q, Mazhar M, Miller LS. Immune and Inflammatory Reponses to Staphylococcus aureus Skin Infections. Curr Dermatol Rep. 2018;7(4):338-49.. Nair D, Memmi G, Hernandez D, Bard J, Beaume M, Gill S, et al. Whole-genome sequencing of Staphylococcus aureus strain RN4220, a key laboratory strain used in virulence research, identifies mutations that affect not only virulence factors but also the fitness of the strain. J Bacteriol. 2011;193(9):2332-5.Sakr A, Brégeon F, Mège J-L, Rolain J-M, Blin O. Staphylococcus aureus nasal colonization: an update on mechanisms, epidemiology, risk factors, and subsequent infections. Frontiers in microbiology. 2018;9:2419.Wertheim HF, Vos MC, Ott A, van Belkum A, Voss A, Kluytmans JA, et al. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet. 2004;364(9435):703-5.Liu GY. Molecular pathogenesis of Staphylococcus aureus infection. Pediatr Res. 2009;65(5 Pt 2):71R7R.Álvarez A, Fernández L, Gutiérrez D, Iglesias B, Rodríguez A, García P. Methicillin-resistant Staphylococcus aureus in hospitals: Latest trends and treatments based on bacteriophages. Journal of Clinical Microbiology. 2019;57(12):e01006-19.Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. Multistate pointprevalence survey of health care–associated infections. New England Journal of Medicine. 2014;370(13):1198- 208.Jones MJ, Donegan NP, Mikheyeva IV, Cheung AL. Improving transformation of Staphylococcus aureus belonging to the CC1, CC5 and CC8 clonal complexes. PloS one. 2015;10(3).Choo EJ. Community-Associated Methicillin-Resistant Staphylococcus aureus in Nosocomial Infections. Infect Chemother. 2017;49(2):158-9Kateete DP, Bwanga F, Seni J, Mayanja R, Kigozi E, Mujuni B, et al. CA-MRSA and HA-MRSA coexist in community and hospital settings in Uganda. Antimicrobial Resistance & Infection Control. 2019;8(1):1-9.Enright MC, Day NP, Davies CE, Peacock SJ, Spratt BG. Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. Journal of clinical microbiology. 2000;38(3):1008-15.Grundmann H, Aanensen DM, van den Wijngaard CC, Spratt BG, Harmsen D, Friedrich AW. Geographic distribution of Staphylococcus aureus causing invasive infections in Europe: a molecular-epidemiological analysis. PLoS Med. 2010;7(1):e1000215.Jian Y, Zhao L, Zhao N, Lv HY, Liu Y, He L, et al. Increasing prevalence of hypervirulent ST5 methicillin susceptible Staphylococcus aureus subtype poses a serious clinical threat. Emerg Microbes Infect. 2021;10(1):109-22.McCarthy H, Rudkin JK, Black NS, Gallagher L, O'Neill E, O'Gara JP. Methicillin resistance and the biofilm phenotype in Staphylococcus aureus. Front Cell Infect Microbiol. 2015;5:1.Vázquez Núñez JC. 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Predicting the Staphylococcus aureus nasal carrier state: derivation and validation of a “culture rule”. Clinical Infectious Diseases. 2004;39(6):806-11.van Belkum A, Verkaik NJ, De Vogel CP, Boelens HA, Verveer J, Nouwen JL, et al. Reclassification of Staphylococcus aureus nasal carriage types. The Journal of infectious diseases. 2009;199(12):1820-6Flores R, Villarroel JL, Valenzuela F. Enfrentamiento de las infecciones de piel en el adulto. Revista Médica Clínica Las Condes. 2021;32(4):429-41.Lamaro-Cardoso J, de Lencastre H, Kipnis A, Pimenta FC, Oliveira LS, Oliveira RM, et al. Molecular epidemiology and risk factors for nasal carriage of Staphylococcus aureus and methicillin-resistant S. aureus in infants attending day care centers in Brazil. Journal of clinical microbiology. 2009;47(12):3991-7.Ellis MW, Griffith ME, Jorgensen JH, Hospenthal DR, Mende K, Patterson JE. Presence and molecular epidemiology of virulence factors in methicillin-resistant Staphylococcus aureus strains colonizing and infecting soldiers. Journal of clinical microbiology. 2009;47(4):940-5.Lear A, McCord G, Peiffer J, Watkins RR, Parikh A, Warrington S. Incidence of Staphylococcus aureus nasal colonization and soft tissue infection among high school football players. The Journal of the American Board of Family Medicine. 2011;24(4):429-35.Saxena S, Goyal R, Das S, Mathur M, Talwar V. Prevalence of methicillin-resistant Staphylococcus aureus colonization among healthcare workers and healthy community residents. Journal of Health, Population and Nutrition. 2002:279-80.Cohn LA, Middleton JR. A veterinary perspective on methicillin‐resistant staphylococci. Journal of veterinary emergency and critical care. 2010;20(1):31-45.Rivera Romero FJ. Portafolio de la experiencia durante el Internado Médico en el período junio 2021 a febrero 2022 en los establecimientos de salud: Hospital Nacional Dos de Mayo y Centro Materno Infantil Ollantay.Castillo Higgins MV. Prevalencia de bacteriemia y sus complicaciones por Staphylococcus aureus en pacientes atendidos en el Hospital Roberto Gilbert Elizalde en el período enero 2018-diciembre 2019. 2020.Sollid JUE, Furberg AS, Hanssen AM, Johannessen M. Staphylococcus aureus: determinants of human carriage. Infection, genetics and evolution. 2014;21:531-41.Graham III PL, Lin SX, Larson EL. A US population-based survey of Staphylococcus aureus colonization. Annals of internal medicine. 2006;144(5):318-25.Lebon A, Labout J, Verbrugh HA, Jaddoe V, Hofman A, van Wamel W, et al. Dynamics and determinants of Staphylococcus aureus carriage in infancy: the Generation R Study. Bacterial carriage in infancy Risk factors and consequences The Generation R study. 2010;46(10):43.Pastacaldi C, Lewis P, Howarth P. Staphylococci and staphylococcal superantigens in asthma and rhinitis: a systematic review and meta‐analysis. Allergy. 2011;66(4):549-55Crum-Cianflone NF, Shadyab AH, Weintrob A, Hospenthal DR, Lalani T, Collins G, et al. Association of methicillin-resistant Staphylococcus aureus (MRSA) colonization with high-risk sexual behaviors in persons infected with human immunodeficiency virus (HIV). Medicine. 2011;90(6):379-89.Ruimy R, Angebault C, Djossou F, Dupont C, Epelboin L, Jarraud S, et al. Are host genetics the predominant determinant of persistent nasal Staphylococcus aureus carriage in humans? The Journal of infectious diseases. 2010;202(6):924-34.Verkaik NJ, de Vogel CP, Boelens HA, Grumann D, Hoogenboezem T, Vink C, et al. Anti-staphylococcal humoral immune response in persistent nasal carriers and noncarriers of Staphylococcus aureus. 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Caracterización de factores inmunológicos y microbiológicos asociados a la colonización e infección por Staphylococcus aureus

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