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In vitro evolution of Pseudomonas aeruginosa AA2 biofilms in the presence of cystic fibrosis lung microbiome members.

ABSTRACT: In cystic fibrosis (CF) airways, the opportunistic pathogen Pseudomonas aeruginosa evolves from an acute to a chronic infection phenotype. Yet, the in vivo factors influencing the evolutionary trajectory of P. aeruginosa are poorly understood. This study aimed at understanding the role of the CF lung microbiome in P. aeruginosa evolution. Therefore, we investigated the in vitro biofilm evolution of an early CF P. aeruginosa isolate, AA2, in the presence or absence of a synthetic CF lung microbiome. Whole genome sequencing of evolved populations revealed mutations in quorum sensing (QS) genes (lasR, pqsR) with and without the microbiome. Phenotypic assays confirmed decreased production of the QS molecule 3-O-C12-homoserine lactone, and QS-regulated virulence factors pyocyanin and protease. Furthermore, a mixture of lasR and lasR pqsR mutants was found, in which double mutants showed less pyocyanin and protease production than lasR mutants. While the microbial community did not influence the production of the tested P. aeruginosa virulence factors, we observed a trend towards more mutations in the transcriptional regulators gntR and mexL when P. aeruginosa was grown alone. P. aeruginosa developed resistance to ?-lactam antibiotics during evolution, when grown with and without the microbiome. In conclusion, in an experimental biofilm environment, the early P. aeruginosa CF isolate AA2 evolves towards a CF-like genotype and phenotype, and most studied evolutionary adaptations are not impacted by CF microbiome members.

SUBMITTER: Vandeplassche E

PROVIDER: S-EPMC6731285 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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In vitro evolution of Pseudomonas aeruginosa AA2 biofilms in the presence of cystic fibrosis lung microbiome members.

Vandeplassche Eva E Sass Andrea A Lemarcq Astrid A Dandekar Ajai A AA Coenye Tom T Crabbé Aurélie A

Scientific reports 20190906 1

In cystic fibrosis (CF) airways, the opportunistic pathogen Pseudomonas aeruginosa evolves from an acute to a chronic infection phenotype. Yet, the in vivo factors influencing the evolutionary trajectory of P. aeruginosa are poorly understood. This study aimed at understanding the role of the CF lung microbiome in P. aeruginosa evolution. Therefore, we investigated the in vitro biofilm evolution of an early CF P. aeruginosa isolate, AA2, in the presence or absence of a synthetic CF lung microbio ...[more]

PMID: 31492943

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Project description:UNLABELLED: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.

Dataset Information

In vitro evolution of Pseudomonas aeruginosa AA2 biofilms in the presence of cystic fibrosis lung microbiome members.

Publications

In vitro evolution of Pseudomonas aeruginosa AA2 biofilms in the presence of cystic fibrosis lung microbiome members.

Similar Datasets

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