Investigation of the Mechanism and Chemistry Underlying Staphylococcus aureus<i>'</i> Ability to Inhibit Pseudomonas aeruginosa Growth <i>In Vitro</i>.

Pseudomonas aeruginosa inhibits or eradicates Staphylococcus aureus in most in vitro settings. Nonetheless, P. aeruginosa and S. aureus are commonly isolated from chronically infected, nonhealing wounds and lungs of people with cystic fibrosis (CF). Therefore, we hypothesized that S. aureus could protect itself from P. aeruginosa through glucose-derived metabolites, such as small organic acids, preventing it from being eradicated. This <i>in vitro</i> study demonstrated that S. aureus populations, in the presence of glucose, secrete one or more substances that efficiently eradicate P. aeruginosa in a concentration-dependent manner. These substances had a molecular mass lower than three kDa, were hydrophilic, heat- and proteinase-resistant, and demonstrated a pH-dependent effect. Nuclear magnetic resonance analysis identified acetoin, acetic acid, and oligopeptides or cyclic peptides in glucose-grown S. aureus supernatants. All the tested wild-type and clinical S. aureus strain inhibited P. aeruginosa growth. Thus, we proposed a model in which a cocktail of these compounds, produced by established S. aureus populations in glucose presence, facilitated these two species' coexistence in chronic infections. <b>IMPORTANCE</b> Chronic infections affect a growing part of the population and are associated with high societal and personal costs. Multiple bacterial species are often present in these infections, and multispecies infections are considered more severe than single-species infections. Staphylococcus aureus and Pseudomonas aeruginosa often coexist in chronic infections. However, the interactions between these two species and their coexistence in chronic infections are not fully understood. By exploring in vitro interactions, we found a novel S. aureus-mediated inhibition of P. aeruginosa, and we suggested a model of the coexistence of the two species in chronic infections. With this study, we enhanced our understanding of the pathogenesis of chronic multispecies infections, which is crucial to paving the way for developing improved treatment strategies.