Pseudomonas aeruginosa exoproducts determine antibiotic efficacy against Staphylococcus aureus

Abstract

Chronic coinfections of Staphylococcus aureus and Pseudomonas aeruginosa frequently fail to respond to antibiotic treatment, leading to significant patient morbidity and mortality. Currently, the impact of interspecies interaction on S. aureus antibiotic susceptibility remains poorly understood. In this study, we utilize a panel of P. aeruginosa burn wound and cystic fibrosis (CF) lung isolates to demonstrate that P. aeruginosa alters S. aureus susceptibility to bactericidal antibiotics in a variable, strain-dependent manner and further identify 3 independent interactions responsible for antagonizing or potentiating antibiotic activity against S. aureus. We find that P. aeruginosa LasA endopeptidase potentiates lysis of S. aureus by vancomycin, rhamnolipids facilitate proton-motive force-independent tobramycin uptake, and 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) induces multidrug tolerance in S. aureus through respiratory inhibition and reduction of cellular ATP. We find that the production of each of these factors varies between clinical isolates and corresponds to the capacity of each isolate to alter S. aureus antibiotic susceptibility. Furthermore, we demonstrate that vancomycin treatment of a S. aureus mouse burn infection is potentiated by the presence of a LasA-producing P. aeruginosa population. These findings demonstrate that antibiotic susceptibility is complex and dependent not only upon the genotype of the pathogen being targeted, but also on interactions with other microorganisms in the infection environment. Consideration of these interactions will improve the treatment of polymicrobial infections.

Allelic polymorphism shapes community function in evolving Pseudomonas aeruginosa populations

“…Studies on P. aeruginosa populations isolated from individual lungs, have demonstrated divergent evolution, resulting in heterogeneous populations of P. aeruginosa within patients (16,17,19). This genetic adaptation and diversification is likely to impact on levels of pathogenicity and the efficacy of antibiotic treatment (16,20), and could potentially impact how other species of microbe colonize the CF lung (4,(21)(22)(23)(24)(25)(26)(27).…”

Bidirectional alterations in antibiotics susceptibility in Staphylococcus aureus - Pseudomonas aeruginosa dual-species biofilm

“…In the meanwhile, the observed reduction of the S. aureus CFUs number was not a consequence of their transition into small colony variants in response to aminoglycosides and cyanide production by P. aeruginosa (see Figs S15, S16). Apparently, this effect could be attributed to rhamnolipids synthesis with P. aeruginosa which increase S. aureus susceptibility to aminoglycosides 81 .…”

“…In several works the alteration of S. aureus susceptibility to various antimicrobials in presence of P. aeruginosa has been shown mainly in liquid cultures 21,81,82 . Here, we investigated the effect of two groups of antimicrobials on bacterial viability in mixed biofilms.…”

Exogenous alginate protectsStaphylococcus aureusfrom killing byPseudomonas aeruginosa

“…Pseudomonas aeruginosa and Staphylococcus aureus are the two opportunistic pathogens most commonly isolated from CF patients’ lungs (2), and co-infection with both microbes is common (23, 24). Co-infection with P. aeruginosa and S. aureus alters antibiotic tolerance (25–28) and enhances virulence (29) in chronic infection. Furthermore, CF patients who are co-infected with both P. aeruginosa and S. aureus have poorer clinical outcomes than those who are mono-infected (23).…”