The study shows that in cystic fibrosis lungs, two types of Pseudomonas bacteria help each other survive: the slimy, alginate‑producing kind shields the other from the human antimicrobial peptide LL‑37, while the non‑slimy kind protects the slimy bacteria from hydrogen peroxide by sharing an enzyme called catalase.

<i>Pseudomonas aeruginosa</i> causes chronic pulmonary infections in patients with cystic fibrosis (CF). <i>P.&#xa0;aeruginosa</i> mucoid conversion, defined by overproduction of the exopolysaccharide alginate, correlates with accelerated decline in CF patient lung function. Recalcitrance of the mucoid phenotype to clearance by antibiotics and the immune response is well documented. However, despite advantages conferred by mucoidy, mucoid variants often revert to a nonmucoid phenotype both <i>in vitro</i> and <i>in vivo</i> Mixed populations of mucoid isolates and nonmucoid revertants are recovered from CF lungs, suggesting a selective benefit for coexistence of these variants. In this study, cocultures of mucoid and nonmucoid variants exhibited enhanced resistance to two host antimicrobials: LL-37, a cationic antimicrobial peptide, and hydrogen peroxide (H₂O₂). Alginate production by mucoid isolates protected nonmucoid variants in consortia from LL-37, as addition of alginate exogenously to nonmucoid variants abrogated LL-37 killing. Conversely, nonmucoid revertants shielded mucoid variants from H₂O₂ stress via catalase (KatA) production, which was transcriptionally repressed by AlgT and AlgR, central regulators of alginate biosynthesis. Furthermore, extracellular release of KatA by nonmucoid revertants was dependent on <i>lys</i>, encoding an endolysin implicated in autolysis and extracellular DNA (eDNA) release. Overall, these data provide a rationale to study interactions of <i>P.&#xa0;aeruginosa</i> mucoid and nonmucoid variants as contributors to evasion of innate immunity and persistence within the CF lung.<b>IMPORTANCE</b><i>P.&#xa0;aeruginosa</i> mucoid conversion within lungs of cystic fibrosis (CF) patients is a hallmark of chronic infection and predictive of poor prognosis. The selective benefit of mixed populations of mucoid and nonmucoid variants, often isolated from chronically infected CF patients, has not been explored. Here, we show that mixed-variant communities of <i>P.&#xa0;aeruginosa</i> demonstrate advantages in evasion of innate antimicrobials via production of shared goods: alginate and catalase. These data argue for therapeutically targeting multiple constituents (both mucoid and nonmucoid variants) within diversified <i>P.&#xa0;aeruginosa</i> communities <i>in vivo</i>, as these variants can differentially shield one another from components of the host response.