Role of R5 pyocin in the predominance of high-risk Pseudomonas aeruginosa isolates
Liyang Zhang1, Qi Xu2, Filemon C Tan1
1Department of BioSciences, Rice University, Houston, TX, United States.
Abstract:
Infections with antimicrobial-resistant pathogens, such as Pseudomonas aeruginosa, are a frequent occurrence in healthcare settings. Although human P. aeruginosa infections are predominantly caused by a small number of sequence types (ST), such as ST235 and ST111, that are frequently multidrug-resistant, the basis for this dominance remains unclear. Using a genome-wide, transposon-insertion library screen, we discovered that the production of R5 pyocins (one of 5 subtypes of R pyocins) confers a competitive advantage to ST111 strains. Competitive dominance was lost by mutants lacking R pyocin production. Analysis of 5135 P. aeruginosa strains revealed that several international, high-risk sequence types (including ST235 and ST111) are enriched for R5 pyocin production, indicating a correlation between R5 pyocin production and clinical dominance, suggesting a novel approach for evaluating risk from emerging P. aeruginosa strains. An ST235 strain also lost its competitive advantage after deletion of an R5 pyocin structural gene, corroborating these findings. Overall, our study sheds light onto mechanisms underlying predominance of particular clades of antimicrobial resistant bacteria.
Insights
The production of R5 pyocins gives certain Pseudomonas aeruginosa strains a competitive edge, explaining their dominance in healthcare settings. This finding could help identify high-risk bacterial strains.
Area of Science:
- Microbiology
- Genetics
- Epidemiology
Background:
- Antimicrobial resistance is a major healthcare challenge.
- Pseudomonas aeruginosa, particularly multidrug-resistant strains like ST235 and ST111, frequently causes infections in healthcare settings.
- The reasons for the dominance of specific P. aeruginosa sequence types (STs) are not fully understood.
Purpose of the Study:
- To investigate the genetic basis for the clinical dominance of specific Pseudomonas aeruginosa sequence types.
- To identify factors contributing to the competitive advantage of high-risk P. aeruginosa strains.
Main Methods:
- Genome-wide transposon-insertion library screening was employed to identify genes conferring a competitive advantage.
- Mutagenesis studies were performed by deleting R5 pyocin genes in ST111 and ST235 strains.
- Analysis of a large collection of 5135 P. aeruginosa strains was conducted.
Main Results:
- Production of R5 pyocins was found to confer a significant competitive advantage to ST111 P. aeruginosa strains.
- Mutants lacking R5 pyocin production lost their competitive dominance.
- Several international high-risk P. aeruginosa sequence types, including ST235 and ST111, showed enrichment for R5 pyocin production.
- Deletion of an R5 pyocin structural gene in an ST235 strain resulted in loss of competitive advantage.
Conclusions:
- R5 pyocin production is a key factor contributing to the clinical dominance of specific high-risk Pseudomonas aeruginosa sequence types.
- This finding suggests a potential mechanism for evaluating the risk posed by emerging P. aeruginosa strains.
- Understanding these mechanisms is crucial for combating antimicrobial resistance in clinical settings.
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