High prevalence of lipopolysaccharide mutants and R2-Pyocin susceptible variants in Pseudomonas aeruginosa populations sourced from cystic fibrosis lung infections

• Authors: Madeline Mei, Georgia Institute of Technology, Atlanta; Preston Pheng, Georgia Institute of Technology, Atlanta; Detriana Kurzeja-Edwards, Georgia Institute of Technology, Atlanta; Stephen P Diggle, Georgia Institute of Technology, Atlanta,
• Journal Title: bioRxiv
• Volume: Volume 2023
• Publisher: NIH | 2023-04-28
• Type of Work: Article | Preprint: Prior to Peer Review
• Publisher DOI: http://doi.org/10.1101/2023.04.26.538445
• Subjects: Health Sciences, Immunology; Health Sciences, Medicine and Surgery
• Keywords: R-pyocin; bacteriocin; Pseudomonas aeruginosa; cystic fibrosis; lipopolysaccharide

Abstract

Pseudomonas aeruginosa is a prevalent pathogen in cystic fibrosis (CF) lungs which displays strong resistance to various antibiotic classes, contributing to antimicrobial resistance (AMR). P aeruginosa populations in CF lungs exhibit considerable genetic and phenotypic diversity, raising questions about their susceptibility to non-traditional antimicrobials, such as bacteriocins. R-pyocins, bacteriocins produced by P. aeruginosa, are highly potent, non-replicating phage tail-like protein complexes with a narrow killing spectrum. The diversity of P. aeruginosa variants within CF lung infections may lead to varying susceptibility to R-pyocins due to changes in the lipopolysaccharide (LPS) structure, which acts as the R-pyocin receptor. However, the extent of susceptibility to the five known R-pyocin subtypes (R1-R5) remains unknown, especially considering the diverse P. aeruginosa populations in CF lungs. Additionally, the connection between LPS phenotype and R-pyocin susceptibility is not well understood. We tested 139 P. aeruginosa variants from 17 sputum samples of seven CF patients for R2-pyocin susceptibility and analyzed their LPS phenotypes. Our findings revealed that approximately 83% of sputum samples contained diverse P. aeruginosa populations without R2-pyocin resistant variants, while all samples had some susceptible variants. Moreover, there was no clear correlation between LPS phenotypes and R-pyocin susceptibility. The absence of a clear correlation between LPS phenotypes and R-pyocin susceptibility suggests that LPS packing density may significantly influence R-pyocin susceptibility among CF variants. Our research supports the potential use of R-pyocins as therapeutic agents, as numerous infectious CF variants appear to be susceptible to R2-pyocins, even within diverse P. aeruginosa populations.