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bioRxiv · 10.1101/2024.10.07.616987

Role of R5 Pyocin in the Predominance of High-Risk Pseudomonas aeruginosa Isolates

Zhang, L.·Xu, Q.·Tan, F. C.·Deng, Y.·Hakki, M.·Shelburne, S.·Kirienko, N.
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Abstract

Infections with antimicrobial resistant pathogens, such as Pseudomonas aeruginosa, are a frequent occurrence in healthcare settings. Human P. aeruginosa infections are predominantly caused by a small number of sequence types (ST), such as ST235, ST111, and ST175. Although ST111 is recognized as one of the most prevalent high-risk P. aeruginosa clones worldwide and frequently exhibits multidrug-resistant or extensively drug-resistant phenotypes, the basis for this dominance remains unclear. In this study, we used a genome-wide transposon insertion library screen to discover that the competitive advantage of ST111 strains over certain non-ST111 strains is through production of R pyocins. We confirmed this finding by showing that competitive dominance was lost by ST111 mutants with R pyocin gene deletions. Further investigation showed that sensitivity to ST111 R pyocin (specifically R5 pyocin) is caused by deficiency in the O-antigen ligase waaL, which leaves lipopolysaccharide (LPS) bereft of O antigen, enabling pyocins to bind the LPS core. In contrast, sensitivity of waaL mutants to R1 or R2 pyocins depended on additional genomic changes. In addition, we found the PA14 mutants in lipopolysaccharide biosynthesis (waaL, wbpL, wbpM) that cause high susceptibility to R pyocins also exhibit poor swimming motility. Analysis of 5,135 typed P. aeruginosa strains revealed that several international, high-risk sequence types (including ST235, ST111, and ST175) are enriched for R5 pyocin production, indicating a correlation between these phenotypes and suggesting a novel approach for evaluating risk from emerging prevalent P. aeruginosa strains. Overall, our study sheds light on the mechanisms underlying the dominance of ST111 strains and highlighting the role of waaL in extending spectrum of R pyocin susceptibility.

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Zhang, L., Xu, Q., Tan, F. C., Deng, Y., Hakki, M., Shelburne, S., Kirienko, N.. 2024-10-07. Role of R5 Pyocin in the Predominance of High-Risk Pseudomonas aeruginosa Isolates. https://doi.org/10.1101/2024.10.07.616987

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