Genome-wide network of antibiotic susceptibility in Pseudomonas aeruginosa.

BACKGROUND AND OBJECTIVE: Pseudomonas aeruginosa is a ubiquitous Gram-negative pathogen notorious for causing infections with high mortality rates. Its large genome supports extensive metabolic diversity and promotes its adaptation to diverse environments. The survival and persistence of P. aeruginosa in clinical settings is further facilitated by a vast arsenal of strategies that contribute to its tolerance or resistance to antibiotics. Here, we aimed to systematically identify the genetic determinants that affect its susceptibility to antibiotics.

METHODS: The ordered PA14 transposon mutant library was grown in the presence of sub-MIC concentrations of a panel of antibiotics of various classes, and the growth of each mutant was quantified to generate susceptibility scores.

RESULTS: We observed a dense network of genes affecting antibiotic susceptibility in P. aeruginosa, where a large portion of genes modulated susceptibility to various classes of antibiotics. Not surprisingly, efflux and outer membrane permeability were key contributors, but we also identified genes that are not typically associated with antibiotic susceptibility.

CONCLUSIONS: The data provide a genome-wide view of the antibiotic susceptibility network in P. aeruginosa. Overall, our approach deepens our understanding of antibiotic susceptibility and opens new avenues for developing strategies against multidrug-resistant P. aeruginosa.