An effective response to respiratory inhibition by a <i>Pseudomonas aeruginosa</i> excreted quinoline promotes <i>Staphylococcus aureus</i> fitness and survival in co-culture

Cystic fibrosis is a hereditary respiratory disease that predisposes patients to bacterial infections, often caused by <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>. Secondary metabolites excreted by <i>P. aeruginosa</i> decrease <i>S. aureus</i> fitness during co-infection, ultimately eliminating it. The regulatory systems and mechanisms that <i>S. aureus</i> uses to detect and respond to these metabolites are unknown. The data presented demonstrate that two regulatory systems that are stimulated by alterations in membrane or cytosolic redox status respond to the <i>P. aeruginosa</i>-produced respiratory toxin 2-heptyl-4-quinolone N-oxide (HQNO) by increasing transcription of genes utilized for fermentation, thereby promoting fitness. This study describes interactions between these two bacterial pathogens that could be exploited to decrease pathogen burden in individuals living with cystic fibrosis.