Análisis comparativo de los elementos genómicos de resistencia a antibióticos betalactámicos en cepas colombianas de Providencia rettgeri durante el período 2015 - 2016
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Piza-Buitrago, Leidy Adriana
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Las infecciones asociadas a la atención en salud (IACS) causadas por microorganismos
multirresistentes se asocian con un incremento en los costos para los sistemas de salud
debido a la estancia prolongada de los pacientes. Providencia rettgeri en los últimos
tiempos se ha convertido en una de las más importantes enterobacterias causante de
IACS en el mundo, debido a su relación con el determinante de resistencia blaNDM-1 y
por los altos niveles de resistencia expresados a los antimicrobianos (RAM), en especial
a los carbapenémicos, agentes considerados de último recurso para el tratamiento de
cepas multirresistentes. Debido a este problema de salud pública, el objetivo de este
estudio fue identificar y evaluar los elementos genómicos de resistencia a antibióticos
betalactámicos en cepas colombianas de P. rettgeri. Para ello se realizó la secuenciación
de genoma completo (WGS) de 28 aislamientos obtenidos en el periodo 2015 – 2016.
Así mismo, se determinó el perfil fenotípico de resistencia, se tipificaron los aislamientos
y se generaron perfiles genómicos de resistencia por medio de un flujo de trabajo
bioinformático, para un posterior análisis epidemiológico. Como resultado se observaron
elevados porcentajes de resistencia a carbapenémicos, cefalosporinas, sulfonamidas y
fluoroquinolonas; se obtuvieron por primera vez 8 rSTs de P. rettgeri circulando en el
país, de los cuales 7 fueron nuevos. Se encontró que el rST-63073 (45%) y rST-61696
(25%) fueron dominantes. También se identificaron 116 genes mediadores de
resistencia, representativos de los mecanismos de resistencia: degradación y
modificación, bombas de eflujo, porinas y cambio del sitio blanco. Finalmente se realizó
el pangenoma para establecer las relaciones filogenéticas y se correlacionó el perfil
genómico obtenido por WGS con el perfil fenotípico de resistencia. El árbol filogenético
indicó la amplia dispersión de las cepas de P. rettgeri en Colombia, la tipificación a partir
de WGS mostró un poder discriminatorio más alto y el estudio por WGS proporcionó
evidencia de un alto nivel de concordancia (96.4%) entre los perfiles fenotípicos y
genotípicos de RAM para predecir resistencia a antibióticos betalactámicos y del (96,8%
- 92,8%) para predecir resistencia a antibióticos No betalactámicos. Los perfiles
genómicos generados en el estudio demostraron ser un determinante importante para
caracterizar los aislamientos con base en el resistoma.
Palabras clave: Providencia rettgeri, Secuenciación de genoma completo (WGS),
resistencia a los antimicrobianos (RAM), perfil fenotípico de resistencia, perfil
genómico de resistencia, Infecciones asociadas a la atención en salud (IACS).
The Healthcare-Associated Infections (HAI) caused by multiresistant microorganisms are associated with an increase in costs for health systems due to the prolonged stay of patients. Providencia rettgeri in recent times has become one of the most important enterobacteria causing HAI in the world, due to its relationship with the determinant of resistance blaNDM-1 and the high levels of resistance expressed to antimicrobials (AMR), especially carbapenems, agents considered of last resort for the treatment of multiresistant strains. Due to this public health problem, the objective of this study was to identify and evaluate the genomic elements of resistance to beta-lactam antibiotics in Colombian strains of P. rettgeri. For this, the whole genome sequencing (WGS) of 28 isolates obtained in the period 2015-2016 was carried out. Likewise, the phenotypic profile of resistance was determined, the isolates were typified and genomic profiles of resistance were generated through of a flow of bioinformatic work, for a later epidemiological analysis. As a result, high percentages of resistance to carbapenems, cephalosporins, sulfonamides and fluoroquinolones were observed; 8 rSTs of P. rettgeri circulating in the country were obtained for the first time, of which 7 were new. It was found that rST-63073 (45%) and rST-61696 (25%) were dominant. We also identified 116 resistance genes, representative of the mechanisms of resistance: degradation and modification, efflux pumps, porins and target alteration. Finally, the pangenome was performed to establish the phylogenetic relationships and the genomic profile obtained by WGS was correlated with the phenotypic profile of resistance. The phylogenetic tree indicated the wide dispersion of the P. rettgeri strains in Colombia, the typing from WGS showed a higher discriminatory power and the WGS study provided evidence of a high level of concordance (96.4%) between the phenotypic and genotypic profiles of RAM to predict resistance to beta-lactam antibiotics and (96.8% - 92.8%) to predict resistance to non-beta-lactam antibiotics. The genomic profiles generated in the study proved to be an important determinant to characterize the isolations based on the resistoma. Keywords: Providencia rettgeri, whole genome sequencing (WGS), Antimicrobial resistance (AMR), phenotypic profile of resistance, genomic profile of resistance, Healthcare-Associated Infections (HAI).
The Healthcare-Associated Infections (HAI) caused by multiresistant microorganisms are associated with an increase in costs for health systems due to the prolonged stay of patients. Providencia rettgeri in recent times has become one of the most important enterobacteria causing HAI in the world, due to its relationship with the determinant of resistance blaNDM-1 and the high levels of resistance expressed to antimicrobials (AMR), especially carbapenems, agents considered of last resort for the treatment of multiresistant strains. Due to this public health problem, the objective of this study was to identify and evaluate the genomic elements of resistance to beta-lactam antibiotics in Colombian strains of P. rettgeri. For this, the whole genome sequencing (WGS) of 28 isolates obtained in the period 2015-2016 was carried out. Likewise, the phenotypic profile of resistance was determined, the isolates were typified and genomic profiles of resistance were generated through of a flow of bioinformatic work, for a later epidemiological analysis. As a result, high percentages of resistance to carbapenems, cephalosporins, sulfonamides and fluoroquinolones were observed; 8 rSTs of P. rettgeri circulating in the country were obtained for the first time, of which 7 were new. It was found that rST-63073 (45%) and rST-61696 (25%) were dominant. We also identified 116 resistance genes, representative of the mechanisms of resistance: degradation and modification, efflux pumps, porins and target alteration. Finally, the pangenome was performed to establish the phylogenetic relationships and the genomic profile obtained by WGS was correlated with the phenotypic profile of resistance. The phylogenetic tree indicated the wide dispersion of the P. rettgeri strains in Colombia, the typing from WGS showed a higher discriminatory power and the WGS study provided evidence of a high level of concordance (96.4%) between the phenotypic and genotypic profiles of RAM to predict resistance to beta-lactam antibiotics and (96.8% - 92.8%) to predict resistance to non-beta-lactam antibiotics. The genomic profiles generated in the study proved to be an important determinant to characterize the isolations based on the resistoma. Keywords: Providencia rettgeri, whole genome sequencing (WGS), Antimicrobial resistance (AMR), phenotypic profile of resistance, genomic profile of resistance, Healthcare-Associated Infections (HAI).
Abstract
Palabras clave propuestas
Providencia rettgeri, Secuenciación de genoma completo (WGS), resistencia a los antimicrobianos (RAM), perfil fenotípico de resistencia, perfil genómico de resistencia, Infecciones asociadas a la atención en salud (IACS).; Providencia rettgeri, whole genome sequencing (WGS), Antimicrobial resistance (AMR), phenotypic profile of resistance, genomic profile of resistance, Healthcare-Associated Infections (HAI).
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Piza-Buitrago Leidy Adriana, 2019. Análisis comparativo de los elementos genómicos de resistencia a antibióticos betalactámicos en cepas colombianas de Providencia rettgeri durante el período 2015 – 2016. Universidad Nacional de Colombia.