Role of R5 pyocin in the predominance of high-risk Pseudomonas aeruginosa isolates

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.