A combination of phenotypic responses and genetic adaptations enables Staphylococcus aureus to withstand inhibitory molecules secreted by Pseudomonas aeruginosa

Abstract

Different bacterial pathogens can co-occur in infections, where they interact with one another and influence disease severity. Previous research showed that pathogens can evolve and adapt to co-infecting species. Here, we show that evolution through genetic mutations and selection is not necessarily required to change pathogen behavior. Instead, we found that the human pathogen Staphylococcus aureus is able to plastically respond to the presence of Pseudomonas aeruginosa , a competing pathogen. Through proteomics and metabolomics, we demonstrate that S. aureus undergoes substantial proteomic alterations in response to P. aeruginosa by downregulating virulence factor expression, changing metabolism, and mounting protective measures against toxic compounds. Our work highlights that pathogens possess sophisticated mechanisms to respond to competitors to secure growth and survival in polymicrobial infections. We predict such plastic responses to have significant impacts on infection outcomes.