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Replication of the Ordered, Nonredundant Library of Pseudomonas aeruginosa strain PA14 Transposon Insertion Mutants
Published on: May 4, 2018
Pseudomonas aeruginosa clinical blood isolates display significant phenotypic variability
Robert J Scheffler1,2, Benjamin P Bratton1,3,4, Zemer Gitai1
1Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
Abstract:
Pseudomonas aeruginosa is a significant threat in healthcare settings where it deploys a wide host of virulence factors to cause disease. Many virulence-related phenotypes such as pyocyanin production, biofilm formation, and twitching motility have been implicated in causing disease in a number of hosts. In this study, we investigate these three virulence factors in a collection of 22 clinical strains isolated from blood stream infections. Despite the fact that all 22 strains caused disease and came from the same body site of different patients, they show significant variability in assays for each of the three specific phenotypes examined. There was no significant correlation between the strength of the three phenotypes across our collection, suggesting that they can be independently modulated. Furthermore, strains deficient in each of the virulence-associated phenotypes examined could be identified. To understand the genetic basis of this variability we sequenced the genomes of the 22 strains. We found that the majority of genes responsible for pyocyanin production, biofilm formation, and twitching motility were highly conserved among the strains despite their phenotypic variability, suggesting that the phenotypic variability is likely due to regulatory changes. Our findings thus demonstrate that no one lab-assayed phenotype of pyocyanin production, biofilm production, and twitching motility is necessary for a P. aeruginosa strain to cause blood stream infection and that additional factors may be needed to fully predict what strains will lead to specific human diseases.
Insights
Pseudomonas aeruginosa strains causing bloodstream infections show varied virulence. Despite conserved genes, phenotypic differences in pyocyanin, biofilm, and motility suggest regulatory control, not just genetic makeup.
Area of Science:
- Microbiology
- Infectious Diseases
- Genomics
Background:
- Pseudomonas aeruginosa is a major healthcare-associated pathogen.
- Virulence factors like pyocyanin, biofilm formation, and twitching motility contribute to P. aeruginosa pathogenicity.
- Understanding the variability of these factors is crucial for infection control.
Purpose of the Study:
- To investigate the variability of pyocyanin production, biofilm formation, and twitching motility in clinical P. aeruginosa strains.
- To explore the genetic basis of observed phenotypic variability.
- To determine the necessity of these specific virulence factors in causing bloodstream infections.
Main Methods:
- Phenotypic assays for pyocyanin production, biofilm formation, and twitching motility.
- Genomic sequencing of 22 clinical P. aeruginosa isolates from bloodstream infections.
- Comparative analysis of virulence factor genes and their conservation.
Main Results:
- Significant phenotypic variability was observed for all three virulence factors among the 22 strains.
- No significant correlation was found between the expression levels of the three phenotypes.
- Genomic analysis revealed high conservation of genes involved in these virulence factors, suggesting regulatory mechanisms drive phenotypic variation.
- Strains deficient in individual virulence factors were identified.
Conclusions:
- Phenotypic variability in P. aeruginosa virulence factors is common and likely regulated post-transcriptionally.
- No single tested virulence factor is essential for causing P. aeruginosa bloodstream infections.
- Predicting P. aeruginosa pathogenicity requires understanding broader genetic and regulatory networks beyond these specific phenotypes.
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