TY - JOUR T1 - Exogenous alginate protects <em>Staphylococcus aureus</em> from killing by <em>Pseudomonas aeruginosa</em> JF - bioRxiv DO - 10.1101/748459 SP - 748459 AU - Courtney E. Price AU - Dustin G. Brown AU - Dominique H. Limoli AU - Vanessa V. Phelan AU - George A. O’Toole Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/08/28/748459.abstract N2 - Cystic fibrosis (CF) patients chronically infected with both Pseudomonas aeruginosa and Staphylococcus aureus have worse health outcomes than patients who are mono-infected with either P. aeruginosa or S. aureus. We showed previously that mucoid strains of P. aeruginosa can co-exist with S. aureus in vitro due to transcriptional downregulation of several toxic exoproducts typically produced by P. aeruginosa, including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline N-oxide). Here we demonstrate that exogenous alginate protects S. aureus from P. aeruginosa in both planktonic and biofilm co-culture models under a variety of nutritional conditions. S. aureus protection in the presence of exogenous alginate is due to transcriptional downregulation of pvdA, a gene required for the production of the iron scavenging siderophore pyoverdine, as well as down-regulation of the PQS (Pseudomonas quinolone signal; 2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that co-culture of mucoid P. aeruginosa with non-mucoid P. aeruginosa can mitigate the killing of S. aureus by the non-mucoid strain of P. aeruginosa, indicating that the mechanism we describe here may function in vivo in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability kill S. aureus at late time points, and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the effects of mucoidy in a strain-specific manner.IMPORTANCE CF patients are chronically infected by polymicrobial communities of microorganisms. The two dominant bacterial pathogens that infect CF patient lungs are P. aeruginosa and S. aureus, with ∼30% of patients co-infected by both species. Patients infected with both P. aeruginosa and S. aureus have worse outcomes than mono-infected patients, and both species persist within the same physical space in the lungs of CF patients. A variety of host and environmental factors have been demonstrated to promote P. aeruginosa-S. aureus co-existence, despite evidence that P. aeruginosa kills S. aureus when these organisms are co-cultured in vitro. Thus, a better understanding of P. aeruginosa-S. aureus interactions, particularly mechanisms by which these microorganisms are able to co-exist in proximal physical space, will lead to better informed treatments for chronic polymicrobial infections. ER -