<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Interstrain Dynamics and Selection of Hyperbiofilm Mutants during a Chronic Infection

ABSTRACT Opportunistic pathogens establishing new infections experience strong selection to adapt, often favoring mutants that persist. Capturing this initial dynamic is critical for identifying the first adaptations that drive pathogenesis. Here we used a porcine full-thickness burn wound model of...

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Autores principales: Erin S. Gloag, Christopher W. Marshall, Daniel Snyder, Gina R. Lewin, Jacob S. Harris, Alfonso Santos-Lopez, Sarah B. Chaney, Marvin Whiteley, Vaughn S. Cooper, Daniel J. Wozniak
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Publicado: American Society for Microbiology 2019
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spelling oai:doaj.org-article:bb09f2057f05467fa4e687b97db7fb562021-11-15T16:22:10Z<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Interstrain Dynamics and Selection of Hyperbiofilm Mutants during a Chronic Infection10.1128/mBio.01698-192150-7511https://doaj.org/article/bb09f2057f05467fa4e687b97db7fb562019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01698-19https://doaj.org/toc/2150-7511ABSTRACT Opportunistic pathogens establishing new infections experience strong selection to adapt, often favoring mutants that persist. Capturing this initial dynamic is critical for identifying the first adaptations that drive pathogenesis. Here we used a porcine full-thickness burn wound model of chronic infection to study the evolutionary dynamics of diverse Pseudomonas aeruginosa infections. Wounds were infected with a mixed community of six P. aeruginosa strains, including the model PA14 strain (PA14-1), and biopsies taken at 3, 14, and 28 days postinfection. Hyperbiofilm-forming rugose small-colony variants (RSCVs) were the earliest and predominant phenotypic variant. These variants were detected on day 3 and persisted, with the majority evolved from PA14-1. Whole-genome sequencing of PA14-1 RSCV isolates revealed driver mutations exclusively in the wsp pathway, conferring hyperbiofilm phenotypes. Several of the wsp mutant RSCVs also acquired CRISPR-Cas adaptive immunity to prophages isolated from the P. aeruginosa wound isolate (B23-2) that was also present in the inoculum. These observations emphasize the importance of interstrain dynamics and the role of lysogenic phages in the survival of an invading pathogen. Rather than being a side effect of chronicity, the rapid rise of RSCVs in wounds is evidence of positive selection on the Wsp chemosensory system to produce mutants with elevated biofilm formation capacity. We predict that RSCVs provide a level of phenotypic diversity to the infecting bacterial community and are common, early adaptations during infections. This would likely have significant consequences for clinical outcomes. IMPORTANCE Bacteria adapt to infections by evolving variants that are more fit and persistent. These recalcitrant variants are typically observed in chronic infections. However, it is unclear when and why these variants evolve. To address these questions, we used a porcine chronic wound model to study the evolutionary dynamics of Pseudomonas aeruginosa in a mixed-strain infection. We isolated hyperbiofilm variants that persisted early in the infection. Interstrain interactions were also observed, where adapted variants acquired CRISPR-mediated immunity to phages. We show that when initiating infection, P. aeruginosa experiences strong positive selection for hyperbiofilm phenotypes produced by mutants of a single chemosensory system, the Wsp pathway. We predict that hyperbiofilm variants are early adaptations to infection and that interstrain interactions may influence bacterial burden and infection outcomes.Erin S. GloagChristopher W. MarshallDaniel SnyderGina R. LewinJacob S. HarrisAlfonso Santos-LopezSarah B. ChaneyMarvin WhiteleyVaughn S. CooperDaniel J. WozniakAmerican Society for MicrobiologyarticleCRISPR-CasPseudomonas aeruginosaRSCVWspbacteriophagesbiofilmsMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution DOAJ
collection DOAJ
language EN
topic CRISPR-Cas
Pseudomonas aeruginosa
RSCV
Wsp
bacteriophages
biofilms
Microbiology
QR1-502
spellingShingle CRISPR-Cas
Pseudomonas aeruginosa
RSCV
Wsp
bacteriophages
biofilms
Microbiology
QR1-502
Erin S. Gloag
Christopher W. Marshall
Daniel Snyder
Gina R. Lewin
Jacob S. Harris
Alfonso Santos-Lopez
Sarah B. Chaney
Marvin Whiteley
Vaughn S. Cooper
Daniel J. Wozniak
<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Interstrain Dynamics and Selection of Hyperbiofilm Mutants during a Chronic Infection
description ABSTRACT Opportunistic pathogens establishing new infections experience strong selection to adapt, often favoring mutants that persist. Capturing this initial dynamic is critical for identifying the first adaptations that drive pathogenesis. Here we used a porcine full-thickness burn wound model of chronic infection to study the evolutionary dynamics of diverse Pseudomonas aeruginosa infections. Wounds were infected with a mixed community of six P. aeruginosa strains, including the model PA14 strain (PA14-1), and biopsies taken at 3, 14, and 28 days postinfection. Hyperbiofilm-forming rugose small-colony variants (RSCVs) were the earliest and predominant phenotypic variant. These variants were detected on day 3 and persisted, with the majority evolved from PA14-1. Whole-genome sequencing of PA14-1 RSCV isolates revealed driver mutations exclusively in the wsp pathway, conferring hyperbiofilm phenotypes. Several of the wsp mutant RSCVs also acquired CRISPR-Cas adaptive immunity to prophages isolated from the P. aeruginosa wound isolate (B23-2) that was also present in the inoculum. These observations emphasize the importance of interstrain dynamics and the role of lysogenic phages in the survival of an invading pathogen. Rather than being a side effect of chronicity, the rapid rise of RSCVs in wounds is evidence of positive selection on the Wsp chemosensory system to produce mutants with elevated biofilm formation capacity. We predict that RSCVs provide a level of phenotypic diversity to the infecting bacterial community and are common, early adaptations during infections. This would likely have significant consequences for clinical outcomes. IMPORTANCE Bacteria adapt to infections by evolving variants that are more fit and persistent. These recalcitrant variants are typically observed in chronic infections. However, it is unclear when and why these variants evolve. To address these questions, we used a porcine chronic wound model to study the evolutionary dynamics of Pseudomonas aeruginosa in a mixed-strain infection. We isolated hyperbiofilm variants that persisted early in the infection. Interstrain interactions were also observed, where adapted variants acquired CRISPR-mediated immunity to phages. We show that when initiating infection, P. aeruginosa experiences strong positive selection for hyperbiofilm phenotypes produced by mutants of a single chemosensory system, the Wsp pathway. We predict that hyperbiofilm variants are early adaptations to infection and that interstrain interactions may influence bacterial burden and infection outcomes.
format article
author Erin S. Gloag
Christopher W. Marshall
Daniel Snyder
Gina R. Lewin
Jacob S. Harris
Alfonso Santos-Lopez
Sarah B. Chaney
Marvin Whiteley
Vaughn S. Cooper
Daniel J. Wozniak
author_facet Erin S. Gloag
Christopher W. Marshall
Daniel Snyder
Gina R. Lewin
Jacob S. Harris
Alfonso Santos-Lopez
Sarah B. Chaney
Marvin Whiteley
Vaughn S. Cooper
Daniel J. Wozniak
author_sort Erin S. Gloag
title <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Interstrain Dynamics and Selection of Hyperbiofilm Mutants during a Chronic Infection
title_short <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Interstrain Dynamics and Selection of Hyperbiofilm Mutants during a Chronic Infection
title_full <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Interstrain Dynamics and Selection of Hyperbiofilm Mutants during a Chronic Infection
title_fullStr <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Interstrain Dynamics and Selection of Hyperbiofilm Mutants during a Chronic Infection
title_full_unstemmed <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Interstrain Dynamics and Selection of Hyperbiofilm Mutants during a Chronic Infection
title_sort <named-content content-type="genus-species">pseudomonas aeruginosa</named-content> interstrain dynamics and selection of hyperbiofilm mutants during a chronic infection
publisher American Society for Microbiology
publishDate 2019
url https://doaj.org/article/bb09f2057f05467fa4e687b97db7fb56
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