Molecular Evolution of Extensively Drug-Resistant (XDR) Pseudomonas aeruginosa Strains From Patients and Hospital Environment in a Prolonged Outbreak
In this study, we aimed to elucidate a prolonged outbreak of extensively drug-resistant (XDR) Pseudomonas aeruginosa, at two adjacent hospitals over a time course of 4 years. Since all strains exhibited a similar antibiotic susceptibility pattern and carried the carbapenemase gene blaVIM, a monoclon...
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doaj-60b9743588464caeb6bb093a026ecc5f2020-11-25T01:13:24ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-08-011010.3389/fmicb.2019.01742444513Molecular Evolution of Extensively Drug-Resistant (XDR) Pseudomonas aeruginosa Strains From Patients and Hospital Environment in a Prolonged OutbreakMichael Buhl0Michael Buhl1Christina Kästle2André Geyer3Ingo B. Autenrieth4Ingo B. Autenrieth5Silke Peter6Silke Peter7Matthias Willmann8Matthias Willmann9Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, GermanyGerman Center for Infection Research, Partner Site Tübingen, Tübingen, GermanyInstitute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, GermanyInstitute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, GermanyInstitute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, GermanyGerman Center for Infection Research, Partner Site Tübingen, Tübingen, GermanyInstitute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, GermanyGerman Center for Infection Research, Partner Site Tübingen, Tübingen, GermanyInstitute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, GermanyGerman Center for Infection Research, Partner Site Tübingen, Tübingen, GermanyIn this study, we aimed to elucidate a prolonged outbreak of extensively drug-resistant (XDR) Pseudomonas aeruginosa, at two adjacent hospitals over a time course of 4 years. Since all strains exhibited a similar antibiotic susceptibility pattern and carried the carbapenemase gene blaVIM, a monoclonal outbreak was assumed. To shed light on the intra-hospital evolution of these strains over time, whole genome sequence (WGS) analysis of 100 clinical and environmental outbreak strains was employed. Phylogenetic analysis of the core genome revealed the outbreak to be polyclonal, rather than monoclonal as initially suggested. The vast majority of strains fell into one of two major clusters, composed of 27 and 59 strains, and their accessory genome each revealed over 400 and 600 accessory genes, respectively, thus indicating an unexpectedly high structural diversity among phylogenetically clustered strains. Further analyses focused on the cluster with 59 strains, representing the hospital from which both clinical and environmental strains were available. Our investigation clearly shows both accumulation and loss of genes occur very frequently over time, as reflected by analysis of protein enrichment as well as functional enrichment. In addition, we investigated adaptation through single nucleotide polymorphisms (SNPs). Among the genes affected by SNPs, there are a multidrug efflux pump (mexZ) and a mercury detoxification operon (merR) with deleterious mutations, potentially leading to loss of repression with resistance against antibiotics and disinfectants. Our results not only confirm WGS to be a powerful tool for epidemiologic analyses, but also provide insights into molecular evolution during an XDR P. aeruginosa hospital outbreak. Genome mutation unveiled a striking genetic plasticity on an unexpectedly high level, mostly driven by horizontal gene transfer. Our study adds valuable information to the molecular understanding of “real-world” Intra-hospital P. aeruginosa evolution and is a step forward toward more personalized medicine in infection control.https://www.frontiersin.org/article/10.3389/fmicb.2019.01742/fullextensive drug resistancesingle-nucleotide polymorphismsSNPsprotein enrichmentfunctional enrichmentmercury |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michael Buhl Michael Buhl Christina Kästle André Geyer Ingo B. Autenrieth Ingo B. Autenrieth Silke Peter Silke Peter Matthias Willmann Matthias Willmann |
spellingShingle |
Michael Buhl Michael Buhl Christina Kästle André Geyer Ingo B. Autenrieth Ingo B. Autenrieth Silke Peter Silke Peter Matthias Willmann Matthias Willmann Molecular Evolution of Extensively Drug-Resistant (XDR) Pseudomonas aeruginosa Strains From Patients and Hospital Environment in a Prolonged Outbreak Frontiers in Microbiology extensive drug resistance single-nucleotide polymorphisms SNPs protein enrichment functional enrichment mercury |
author_facet |
Michael Buhl Michael Buhl Christina Kästle André Geyer Ingo B. Autenrieth Ingo B. Autenrieth Silke Peter Silke Peter Matthias Willmann Matthias Willmann |
author_sort |
Michael Buhl |
title |
Molecular Evolution of Extensively Drug-Resistant (XDR) Pseudomonas aeruginosa Strains From Patients and Hospital Environment in a Prolonged Outbreak |
title_short |
Molecular Evolution of Extensively Drug-Resistant (XDR) Pseudomonas aeruginosa Strains From Patients and Hospital Environment in a Prolonged Outbreak |
title_full |
Molecular Evolution of Extensively Drug-Resistant (XDR) Pseudomonas aeruginosa Strains From Patients and Hospital Environment in a Prolonged Outbreak |
title_fullStr |
Molecular Evolution of Extensively Drug-Resistant (XDR) Pseudomonas aeruginosa Strains From Patients and Hospital Environment in a Prolonged Outbreak |
title_full_unstemmed |
Molecular Evolution of Extensively Drug-Resistant (XDR) Pseudomonas aeruginosa Strains From Patients and Hospital Environment in a Prolonged Outbreak |
title_sort |
molecular evolution of extensively drug-resistant (xdr) pseudomonas aeruginosa strains from patients and hospital environment in a prolonged outbreak |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Microbiology |
issn |
1664-302X |
publishDate |
2019-08-01 |
description |
In this study, we aimed to elucidate a prolonged outbreak of extensively drug-resistant (XDR) Pseudomonas aeruginosa, at two adjacent hospitals over a time course of 4 years. Since all strains exhibited a similar antibiotic susceptibility pattern and carried the carbapenemase gene blaVIM, a monoclonal outbreak was assumed. To shed light on the intra-hospital evolution of these strains over time, whole genome sequence (WGS) analysis of 100 clinical and environmental outbreak strains was employed. Phylogenetic analysis of the core genome revealed the outbreak to be polyclonal, rather than monoclonal as initially suggested. The vast majority of strains fell into one of two major clusters, composed of 27 and 59 strains, and their accessory genome each revealed over 400 and 600 accessory genes, respectively, thus indicating an unexpectedly high structural diversity among phylogenetically clustered strains. Further analyses focused on the cluster with 59 strains, representing the hospital from which both clinical and environmental strains were available. Our investigation clearly shows both accumulation and loss of genes occur very frequently over time, as reflected by analysis of protein enrichment as well as functional enrichment. In addition, we investigated adaptation through single nucleotide polymorphisms (SNPs). Among the genes affected by SNPs, there are a multidrug efflux pump (mexZ) and a mercury detoxification operon (merR) with deleterious mutations, potentially leading to loss of repression with resistance against antibiotics and disinfectants. Our results not only confirm WGS to be a powerful tool for epidemiologic analyses, but also provide insights into molecular evolution during an XDR P. aeruginosa hospital outbreak. Genome mutation unveiled a striking genetic plasticity on an unexpectedly high level, mostly driven by horizontal gene transfer. Our study adds valuable information to the molecular understanding of “real-world” Intra-hospital P. aeruginosa evolution and is a step forward toward more personalized medicine in infection control. |
topic |
extensive drug resistance single-nucleotide polymorphisms SNPs protein enrichment functional enrichment mercury |
url |
https://www.frontiersin.org/article/10.3389/fmicb.2019.01742/full |
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