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The Pseudomonas aeruginosa Transcriptional Landscape Is Shaped by Environmental Heterogeneity and Genetic Variation.

ABSTRACT: UNLABELLED:Phenotypic variability among bacteria depends on gene expression in response to different environments, and it also reflects differences in genomic structure. In this study, we analyzed transcriptome sequencing (RNA-seq) profiles of 151 Pseudomonas aeruginosa clinical isolates under standard laboratory conditions and of one P. aeruginosa type strain under 14 different environmental conditions. Our approach allowed dissection of the impact of the genetic background versus environmental cues on P. aeruginosa gene expression profiles and revealed that phenotypic variation was larger in response to changing environments than between genomically different isolates. We demonstrate that mutations within the global regulator LasR affect more than one trait (pleiotropy) and that the interaction between mutations (epistasis) shapes the P. aeruginosa phenotypic plasticity landscape. Because of pleiotropic and epistatic effects, average genotype and phenotype measures appeared to be uncorrelated in P. aeruginosa. IMPORTANCE:This work links experimental data of unprecedented complexity with evolution theory and delineates the transcriptional landscape of the opportunistic pathogen Pseudomonas aeruginosa. We found that gene expression profiles are most strongly influenced by environmental cues, while at the same time the transcriptional profiles were also shaped considerably by genetic variation within global regulators. The comprehensive set of transcriptomic and genomic data of more than 150 clinical P. aeruginosa isolates will be made publically accessible to all researchers via a dedicated web interface. Both Pseudomonas specialists interested in expression and regulation of specific genes and researchers from other fields with more global interest in the phenotypic and genotypic variation of this important model species can access all information on various levels of detail.

SUBMITTER: Dotsch A

PROVIDER: S-EPMC4488947 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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The Pseudomonas aeruginosa Transcriptional Landscape Is Shaped by Environmental Heterogeneity and Genetic Variation.

Dötsch Andreas A Schniederjans Monika M Khaledi Ariane A Hornischer Klaus K Schulz Sebastian S Bielecka Agata A Eckweiler Denitsa D Pohl Sarah S Häussler Susanne S

mBio 20150630 4

<h4>Unlabelled</h4>Phenotypic variability among bacteria depends on gene expression in response to different environments, and it also reflects differences in genomic structure. In this study, we analyzed transcriptome sequencing (RNA-seq) profiles of 151 Pseudomonas aeruginosa clinical isolates under standard laboratory conditions and of one P. aeruginosa type strain under 14 different environmental conditions. Our approach allowed dissection of the impact of the genetic background versus envir ...[more]

PMID: 26126853

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Project description:UnlabelledMicrobial population polymorphisms are commonly observed in natural environments, including long-term infected hosts. However, the underlying processes promoting and stabilizing diversity are difficult to unravel and are not well understood. Here, we use chronic infection of cystic fibrosis airways by the opportunistic pathogen Pseudomonas aeruginosa as a system for investigating bacterial diversification processes during the course of infection. We analyze clonal bacterial isolates sampled during a 32-year period and map temporal and spatial variations in population diversity to different infection sites within the infected host. We show that the ancestral infecting strain diverged into distinct sublineages, each with their own functional and genomic signatures and rates of adaptation, immediately after initial colonization. The sublineages coexisted in the host for decades, suggesting rapid evolution of stable population polymorphisms. Critically, the observed generation and maintenance of population diversity was the result of partitioning of the sublineages into physically separated niches in the CF airway. The results reveal a complex within-host population structure not previously realized and provide evidence that the heterogeneity of the highly structured and complex host environment promotes the evolution and long-term stability of pathogen population diversity during infection.ImportanceWithin-host pathogen evolution and diversification during the course of chronic infections is of importance in relation to therapeutic intervention strategies, yet our understanding of these processes is limited. Here, we investigate intraclonal population diversity in P. aeruginosa during chronic airway infections in cystic fibrosis patients. We show the evolution of a diverse population structure immediately after initial colonization, with divergence into multiple distinct sublineages that coexisted for decades and occupied distinct niches. Our results suggest that the spatial heterogeneity in CF airways plays a major role in relation to the generation and maintenance of population diversity and emphasize that a single isolate in sputum may not represent the entire pathogen population in the infected individual. A more complete understanding of the evolution of distinct clonal variants and their distribution in different niches could have positive implications for efficient therapy.

Project description:Pseudomonas aeruginosa is an opportunistic pathogen which is evolving resistance to many currently used antibiotics. While much research has been devoted to the roles of pathogenic P. aeruginosa in cystic fibrosis (CF) patients, less is known of its ecological properties. P. aeruginosa dominates the lungs during chronic infection in CF patients, yet its abundance in some environments is less than that of other diverse groups of pseudomonads. Here, we sought to determine if clinical isolates of P. aeruginosa are vulnerable to environmental pseudomonads that dominate soil and water habitats in one-to-one competitions which may provide a source of inhibitory factors. We isolated a total of 330 pseudomonads from diverse habitats of soil and freshwater ecosystems and competed these strains against one another to determine their capacity for antagonistic activity. Over 900 individual inhibitory events were observed. Extending the analysis to P. aeruginosa isolates revealed that clinical isolates, including ones with increased alginate production, were susceptible to competition by multiple environmental strains. We performed transposon mutagenesis on one isolate and identified an ∼14.8-kb locus involved in antagonistic activity. Only two other environmental isolates were observed to carry the locus, suggesting the presence of additional unique compounds or interactions among other isolates involved in outcompeting P. aeruginosa This collection of strains represents a source of compounds that are active against multiple pathogenic strains. With the evolution of resistance of P. aeruginosa to currently used antibiotics, these environmental strains provide opportunities for novel compound discovery against drug-resistant clinical strains.ImportanceWe demonstrate that clinical CF-derived isolates of P. aeruginosa are susceptible to competition in the presence of environmental pseudomonads. We observed that many diverse environmental strains exhibited varied antagonistic profiles against a panel of clinical P. aeruginosa isolates, suggesting the presence of distinct mechanisms of inhibition among these ecological strains. Understanding the properties of these antagonistic events offers the potential for discoveries of antimicrobial compounds or metabolic pathways important to the development of novel treatments for P. aeruginosa infections.

Dataset Information

The Pseudomonas aeruginosa Transcriptional Landscape Is Shaped by Environmental Heterogeneity and Genetic Variation.

Publications

The Pseudomonas aeruginosa Transcriptional Landscape Is Shaped by Environmental Heterogeneity and Genetic Variation.

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