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

Chronic, highly antibiotic-resistant infections in cystic fibrosis (CF)
lungs contribute to increasing morbidity and mortality. Pseudomonas
aeruginosa, a common CF pathogen, exhibits resistance to multiple
antibiotics, contributing to antimicrobial resistance (AMR). These
bacterial populations display genetic and phenotypic diversity, but it is
unclear how this diversity affects susceptibility to bacteriocins.
R-pyocins, i.e. bacteriocins produced by P. aeruginosa, are
phage-tail-like antimicrobials. R-pyocins have potential as
antimicrobials, however, recent research suggests the diversity of P.
aeruginosa variants within CF lung infections leads to varying
susceptibility to R-pyocins. This variation may be linked to changes in
lipopolysaccharide (LPS), acting as the R-pyocin receptor. Currently, it
is unknown how frequently R-pyocin-susceptible strains are in chronic CF
lung infection, particularly when considering the heterogeneity within
these strains. In this study, we tested R2-pyocin susceptibility of 139 P.
aeruginosa variants from 17 sputum samples of seven CF patients and
analyzed LPS phenotypes. We found that 83% of sputum samples did not have
R2-pyocin-resistant variants, while nearly all samples contained
susceptible variants. There was no correlation between LPS phenotype and
R2-pyocin susceptibility, though we estimate that about 76% of
sputum-derived variants lack an O-specific antigen, 40% lack a common
antigen, and 24% have altered LPS cores. The absence of a correlation
between LPS phenotype and R-pyocin susceptibility suggests LPS packing
density may play a significant role in R-pyocin susceptibility among CF
variants. Our research supports the potential of R-pyocins as therapeutic
agents, as many infectious CF variants are susceptible to R2-pyocins, even
within diverse bacterial populations.