Publication: Análisis de elementos genéticos móviles en "Enterococcus faecium": coste biológico e impacto en la diversificación clonal
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2017-05-25
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Universidad Complutense de Madrid
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Abstract
La prevalencia de infecciones hospitalarias causadas por especies del género Enterococcus ha sido baja desde su descripción como patógenos oportunistas al inicio del siglo XX, hasta finales de los años 70s, coincidiendo con la aparición de las primeras cepas resistentes a antibióticos. La especie Enterococcus faecium es actualmente uno de los principales patógenos nosocomiales debido en parte a la alta prevalencia de cepas resistentes a ampicilina y vancomicina. La estructura poblacional de E. faecium ha sido analizada mayoritariamente considerando cepas resistentes a antibióticos y de origen hospitalario pero se desconoce su diversidad en individuos no hospitalizados o de diferentes edades. El conocimiento de los elementos genéticos móviles (EGM) que facilitan la transferencia de genes de resistencia a antibióticos entre clones de la misma o diferente especie, principalmente vancomicina (una de las ultimas opciones terapéuticas para el tratamiento de bacterias Gram positivas multi resistentes a los antibióticos), es también muy reducido. El principal objetivo de esta tesis de doctorado es determinar la influencia en la estructura poblacional y evolvabilidad de E. faecium de los determinantes de resistencia y de los EGM que facilitan su adquisición, transferencia y persistencia. Los capítulos 1 y 2 consisten en el análisis Bayesiano (BAPS) de los datos de MLST procedentes de heces de pacientes hospitalizados y no-hospitalizados de diferentes edades y de aislados de E. faecium causantes de bacteriemias. Este análisis permitió separar los linajes clonales que constituyen el complejo clonal (CC)17 que había sido identificado con la aplicación de metodologías previas en tres líneas clonales de diferente origen, ST18, ST17 y ST78. El aislamiento de cepas de E. faecium pertenecientes a grupos BAPS asociados con la flora comensal humana (BAPS 1 y BAPS 3.3b) sugiere la frecuente adquisición endógena a partir de la microbiota intestinal de las bacteriemias causadas por E. faecium, bien forma directa o a través de infecciones en territorios cercanos (infección urinaria, infección abdominal). Los cambios ocurridos en la microbiota intestinal de los pacientes hospitalizados debido a factores asociados al hospedador (edad) o diferentes presiones selectivas en el medio hospitalario, habrían facilitado la selección (aumento de la densidad poblacional) y la consecuente expansión de las poblaciones de clones de E. faecium resistentes a antibióticos y aumentando por tanto las oportunidades de infección y transmisión de E. faecium...
Enterococci were first known to cause human infections in the early 1900s; however, it was not until the last three decades that they emerged as one of the most important common nosocomial pathogens. Enterococci, and particularly Enterococcus faecium, are now considered as one of the 21st century medical challenges due to the increasing prevalence of multi-drug resistant (MDR) strains, particularly those resistant to ampicillin and vancomycin. The increasing importance of E. faecium as nosocomial pathogen prompted a series of studies regarding its population structure and prevalence of antibiotic resistance particularly in hospitalized patients. Available knowledge regarding the E. faecium populations of community-based humans and individuals of different ages is still scarce. Furthermore, little is known about the mobile genetic elements (MGE) associated with antibiotic resistance determinants, particularly vancomycin, which is one of the last therapeutic options to treat infections caused by multidrug resistant isolates of Gram positive species. As such, the main objective of this PhD dissertation is to assess the influence that antibiotic resistance and more specifically, that of the MGEs associated with ampicillin and vancomycin resistance have had in shaping the population structure and evolution of E. faecium. Chapters 1 and 2 describe the comprehensive analysis of MLST data of E. faecium isolates from faeces of hospitalized and healthy humans of different ages and E. faecium isolates causing bloodstream infections (BSI), via Bayesian Analysis of Population Structure (BAPS) used for analysing the population structure of recombinant bacterial species as E. faecium. Such analysis permitted the identification of differences in the content of enterococcal species at different ages, to confirm that ST18, ST17 and ST78 lineages, previously within CC17, have a separate origin, and to validate the suitability of BAPS for analysing the diversity of E. faecium populations. The recovery from BSI of all E. faecium BAPS groups including those associated with members of the commensal human flora (e.g. BAPS 1 and BAPS 3.3b) pointed out the human gut as the origin of BSI. Changes in the GI tract microbiota of hospitalized patients due to host factors (e.g. age) or different selective pressures in the hospital setting, would have facilitated the selection and the consequent increase in the population size of MDR E. faecium clones, leading to a shift in the composition of E. faecium populations that increases the chances to be infected by MDR and the chances to transmit MDR strains...
Enterococci were first known to cause human infections in the early 1900s; however, it was not until the last three decades that they emerged as one of the most important common nosocomial pathogens. Enterococci, and particularly Enterococcus faecium, are now considered as one of the 21st century medical challenges due to the increasing prevalence of multi-drug resistant (MDR) strains, particularly those resistant to ampicillin and vancomycin. The increasing importance of E. faecium as nosocomial pathogen prompted a series of studies regarding its population structure and prevalence of antibiotic resistance particularly in hospitalized patients. Available knowledge regarding the E. faecium populations of community-based humans and individuals of different ages is still scarce. Furthermore, little is known about the mobile genetic elements (MGE) associated with antibiotic resistance determinants, particularly vancomycin, which is one of the last therapeutic options to treat infections caused by multidrug resistant isolates of Gram positive species. As such, the main objective of this PhD dissertation is to assess the influence that antibiotic resistance and more specifically, that of the MGEs associated with ampicillin and vancomycin resistance have had in shaping the population structure and evolution of E. faecium. Chapters 1 and 2 describe the comprehensive analysis of MLST data of E. faecium isolates from faeces of hospitalized and healthy humans of different ages and E. faecium isolates causing bloodstream infections (BSI), via Bayesian Analysis of Population Structure (BAPS) used for analysing the population structure of recombinant bacterial species as E. faecium. Such analysis permitted the identification of differences in the content of enterococcal species at different ages, to confirm that ST18, ST17 and ST78 lineages, previously within CC17, have a separate origin, and to validate the suitability of BAPS for analysing the diversity of E. faecium populations. The recovery from BSI of all E. faecium BAPS groups including those associated with members of the commensal human flora (e.g. BAPS 1 and BAPS 3.3b) pointed out the human gut as the origin of BSI. Changes in the GI tract microbiota of hospitalized patients due to host factors (e.g. age) or different selective pressures in the hospital setting, would have facilitated the selection and the consequent increase in the population size of MDR E. faecium clones, leading to a shift in the composition of E. faecium populations that increases the chances to be infected by MDR and the chances to transmit MDR strains...
Description
Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Microbiología II, leída el 25-10-2016