R pyocin sensitivity of Pseudomonas aeruginosa clinical isolates from different disease types

Introduction. Multidrug-resistant infections by the opportunistic pathogen Pseudomonas aeruginosa are common in healthcare settings but are increasingly difficult to treat due to high rates of antimicrobial resistance. Hypothesis/Gap Statement. Interest has developed in using R pyocins, bacteriocins produced by P. aeruginosa, as a speciesspecific treatment. We hypothesize that understanding the connections between disease type and R pyocin sensitivity will inform future treatment development. Aim. To evaluate the patterns of R pyocin sensitivity across a library of 247 clinical P. aeruginosa isolates and compare sensitivity profiles of strains when categorizing based on disease type, O-antigen serotype and encoded R pyocin type. Methodology. A combination of genomic analysis and R pyocin sensitivity assays using growth kinetics was conducted on 247 clinical isolates to evaluate genotype, phenotype and disease presentation in the context of R pyocins. Genomic analysis allowed in silico identification of O-antigen serotype and encoded R pyocin type, and phylogenetic comparisons revealed genetic relationships between strains. Results. Comparative analysis of clinical isolates showed that certain conditions, such as chronic infection in the lungs of patients with cystic fibrosis, increased sensitivity to R pyocins. We also observed strong correlations between encoded R pyocin subtype, sensitivity and O-antigen serotype. Finally, our data showed that a large percentage of strains had shared, broadspectrum sensitivity to R pyocins, suggesting that most clinical isolates may be treatable with R pyocins. Conclusion. Our study reveals connections between disease type, O-antigen serotype and R pyocin sensitivity, which may inform future strain analysis and predict the effectiveness of R pyocin treatment.