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

ABSTRACT: Staphylococcus aureus and Pseudomonas aeruginosa frequently co-occur in infections, and there is evidence that their interactions can negatively affect disease outcomes. P. aeruginosa is known to be dominant, often compromising S. aureus through the secretion of inhibitory compounds. We previously demonstrated that S. aureus can become resistant to growth-inhibitory compounds during experimental evolution. While resistance arose rapidly, the underlying mechanisms were not obvious as there were only few genetic mutations associated with resistance, while ample phenotypic changes occurred. We thus hypothesize that resistance may result from phenotypic responses in addition to genetic adaptation. Here, we tested this hypothesis using proteomics. We first focused on an evolved strain that acquired a single mutation in tcyA (encoding a transmembrane transporter unit) upon exposure to P. aeruginosa supernatant. We show that this mutation leads to a complete abolishment of transporter synthesis, which confers moderate protection against PQS and selenocystine, two toxic compounds produced by P. aeruginosa. However, this genetic effect was minor compared to the fundamental phenotypic changes observed at the proteome level when both ancestral and evolved S. aureus strains were exposed to P. aeruginosa supernatant. Major changes involved the downregulation of virulence factors, metabolic pathways and membrane transporters, and the upregulation of ROS scavengers and an efflux pump. Our results suggest that the observed multi-variate phenotypic response is a powerful adaptive strategy by itself, offering instant protection against competitors in fluctuating environments and reducing the need for hard-wired genetic adaptations.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Bacteria Staphylococcus Aureus

SUBMITTER: Jonas Grossmann  

LAB HEAD: Jonas Grossmann

PROVIDER: PXD059647 | Pride | 2025-02-26

REPOSITORIES: Pride