Selective Sweeps and Parallel Pathoadaptation Drive <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Evolution in the Cystic Fibrosis Lung

ABSTRACT Pulmonary infections caused by Pseudomonas aeruginosa are a recalcitrant problem in cystic fibrosis (CF) patients. While the clinical implications and long-term evolutionary patterns of these infections are well studied, we know little about the short-term population dynamics that enable th...

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Autores principales:	Julio Diaz Caballero, Shawn T. Clark, Bryan Coburn, Yu Zhang, Pauline W. Wang, Sylva L. Donaldson, D. Elizabeth Tullis, Yvonne C. W. Yau, Valerie J. Waters, David M. Hwang, David S. Guttman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2789e7aa877341b08cc3bef7161965df
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spelling	oai:doaj.org-article:2789e7aa877341b08cc3bef7161965df2021-11-15T15:41:30ZSelective Sweeps and Parallel Pathoadaptation Drive <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Evolution in the Cystic Fibrosis Lung10.1128/mBio.00981-152150-7511https://doaj.org/article/2789e7aa877341b08cc3bef7161965df2015-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00981-15https://doaj.org/toc/2150-7511ABSTRACT Pulmonary infections caused by Pseudomonas aeruginosa are a recalcitrant problem in cystic fibrosis (CF) patients. While the clinical implications and long-term evolutionary patterns of these infections are well studied, we know little about the short-term population dynamics that enable this pathogen to persist despite aggressive antimicrobial therapy. Here, we describe a short-term population genomic analysis of 233 P. aeruginosa isolates collected from 12 sputum specimens obtained over a 1-year period from a single patient. Whole-genome sequencing and antimicrobial susceptibility profiling identified the expansion of two clonal lineages. The first lineage originated from the coalescence of the entire sample less than 3 years before the end of the study and gave rise to a high-diversity ancestral population. The second expansion occurred 2 years later and gave rise to a derived population with a strong signal of positive selection. These events show characteristics consistent with recurrent selective sweeps. While we cannot identify the specific mutations responsible for the origins of the clonal lineages, we find that the majority of mutations occur in loci previously associated with virulence and resistance. Additionally, approximately one-third of all mutations occur in loci that are mutated multiple times, highlighting the importance of parallel pathoadaptation. One such locus is the gene encoding penicillin-binding protein 3, which received three independent mutations. Our functional analysis of these alleles shows that they provide differential fitness benefits dependent on the antibiotic under selection. These data reveal that bacterial populations can undergo extensive and dramatic changes that are not revealed by lower-resolution analyses. IMPORTANCE Pseudomonas aeruginosa is a bacterial opportunistic pathogen responsible for significant morbidity and mortality in cystic fibrosis (CF) patients. Once it has colonized the lung in CF, it is highly resilient and rarely eradicated. This study presents a deep sampling examination of the fine-scale evolutionary dynamics of P. aeruginosa in the lungs of a chronically infected CF patient. We show that diversity of P. aeruginosa is driven by recurrent clonal emergence and expansion within this patient and identify potential adaptive variants associated with these events. This high-resolution sequencing strategy thus reveals important intraspecies dynamics that explain a clinically important phenomenon not evident at a lower-resolution analysis of community structure.Julio Diaz CaballeroShawn T. ClarkBryan CoburnYu ZhangPauline W. WangSylva L. DonaldsonD. Elizabeth TullisYvonne C. W. YauValerie J. WatersDavid M. HwangDavid S. GuttmanAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 5 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Julio Diaz Caballero Shawn T. Clark Bryan Coburn Yu Zhang Pauline W. Wang Sylva L. Donaldson D. Elizabeth Tullis Yvonne C. W. Yau Valerie J. Waters David M. Hwang David S. Guttman Selective Sweeps and Parallel Pathoadaptation Drive <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Evolution in the Cystic Fibrosis Lung
description	ABSTRACT Pulmonary infections caused by Pseudomonas aeruginosa are a recalcitrant problem in cystic fibrosis (CF) patients. While the clinical implications and long-term evolutionary patterns of these infections are well studied, we know little about the short-term population dynamics that enable this pathogen to persist despite aggressive antimicrobial therapy. Here, we describe a short-term population genomic analysis of 233 P. aeruginosa isolates collected from 12 sputum specimens obtained over a 1-year period from a single patient. Whole-genome sequencing and antimicrobial susceptibility profiling identified the expansion of two clonal lineages. The first lineage originated from the coalescence of the entire sample less than 3 years before the end of the study and gave rise to a high-diversity ancestral population. The second expansion occurred 2 years later and gave rise to a derived population with a strong signal of positive selection. These events show characteristics consistent with recurrent selective sweeps. While we cannot identify the specific mutations responsible for the origins of the clonal lineages, we find that the majority of mutations occur in loci previously associated with virulence and resistance. Additionally, approximately one-third of all mutations occur in loci that are mutated multiple times, highlighting the importance of parallel pathoadaptation. One such locus is the gene encoding penicillin-binding protein 3, which received three independent mutations. Our functional analysis of these alleles shows that they provide differential fitness benefits dependent on the antibiotic under selection. These data reveal that bacterial populations can undergo extensive and dramatic changes that are not revealed by lower-resolution analyses. IMPORTANCE Pseudomonas aeruginosa is a bacterial opportunistic pathogen responsible for significant morbidity and mortality in cystic fibrosis (CF) patients. Once it has colonized the lung in CF, it is highly resilient and rarely eradicated. This study presents a deep sampling examination of the fine-scale evolutionary dynamics of P. aeruginosa in the lungs of a chronically infected CF patient. We show that diversity of P. aeruginosa is driven by recurrent clonal emergence and expansion within this patient and identify potential adaptive variants associated with these events. This high-resolution sequencing strategy thus reveals important intraspecies dynamics that explain a clinically important phenomenon not evident at a lower-resolution analysis of community structure.
format	article
author	Julio Diaz Caballero Shawn T. Clark Bryan Coburn Yu Zhang Pauline W. Wang Sylva L. Donaldson D. Elizabeth Tullis Yvonne C. W. Yau Valerie J. Waters David M. Hwang David S. Guttman
author_facet	Julio Diaz Caballero Shawn T. Clark Bryan Coburn Yu Zhang Pauline W. Wang Sylva L. Donaldson D. Elizabeth Tullis Yvonne C. W. Yau Valerie J. Waters David M. Hwang David S. Guttman
author_sort	Julio Diaz Caballero
title	Selective Sweeps and Parallel Pathoadaptation Drive <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Evolution in the Cystic Fibrosis Lung
title_short	Selective Sweeps and Parallel Pathoadaptation Drive <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Evolution in the Cystic Fibrosis Lung
title_full	Selective Sweeps and Parallel Pathoadaptation Drive <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Evolution in the Cystic Fibrosis Lung
title_fullStr	Selective Sweeps and Parallel Pathoadaptation Drive <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Evolution in the Cystic Fibrosis Lung
title_full_unstemmed	Selective Sweeps and Parallel Pathoadaptation Drive <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Evolution in the Cystic Fibrosis Lung
title_sort	selective sweeps and parallel pathoadaptation drive <named-content content-type="genus-species">pseudomonas aeruginosa</named-content> evolution in the cystic fibrosis lung
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/2789e7aa877341b08cc3bef7161965df
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Selective Sweeps and Parallel Pathoadaptation Drive <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Evolution in the Cystic Fibrosis Lung

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