Pseudomonas aeruginosa Alginate Overproduction Promotes Coexistence with Staphylococcus aureus in a Model of Cystic Fibrosis Respiratory Infection

While complex intra- and interspecies microbial community dynamics are apparent during chronic infections and likely alter patient health outcomes, our understanding of these interactions is currently limited. For example, and are often found to coinfect the lungs of patients with cystic fibrosis (CF), yet these organisms compete under laboratory conditions. Recent observations that coinfection correlates with decreased health outcomes necessitate we develop a greater understanding of these interbacterial interactions. In this study, we tested the hypothesis that and/or adopts phenotypes that allow coexistence during infection. We compared competitive interactions of and isolates from mono- or coinfected CF patients employing coculture models. isolates from monoinfected patients were more competitive toward than isolates from coinfected patients. We also observed that the least competitive isolates possessed a mucoid phenotype. Mucoidy occurs upon constitutive activation of the sigma factor AlgT/U, which regulates synthesis of the polysaccharide alginate and dozens of other secreted factors, including some previously described to kill Here, we show that production of alginate in mucoid strains is sufficient to inhibit anti- activity independent of activation of the AlgT regulon. Alginate reduces production of siderophores, 2-heptyl-4-hydroxyquinolone- -oxide (HQNO), and rhamnolipids-each required for efficient killing of These studies demonstrate alginate overproduction may be an important factor driving coinfection with Numerous deep-sequencing studies have revealed the microbial communities present during respiratory infections in cystic fibrosis (CF) patients are diverse, complex, and dynamic. We now face the challenge of determining the influence of these community dynamics on patient health outcomes and identifying candidate targets to modulate these interactions. We make progress toward this goal by determining that the polysaccharide alginate produced by mucoid strains of is sufficient to inhibit multiple secreted antimicrobial agents produced by this organism. Importantly, these secreted factors are required to outcompete , when the microbes are grown in coculture; thus we propose a mechanism whereby mucoid can coexist with Finally, the approach used here can serve as a platform to investigate the interactions among other CF pathogens.