mixed communities of mucoid and nonmucoid pseudomonas aeruginosa exhibit enhanced resistance to host antimicrobials

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ID: 170241
2018
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Abstract
Pseudomonas aeruginosa causes chronic pulmonary infections in patients with cystic fibrosis (CF). P. aeruginosa 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 in vitro and in vivo. 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 lys, encoding an endolysin implicated in autolysis and extracellular DNA (eDNA) release. Overall, these data provide a rationale to study interactions of P. aeruginosa mucoid and nonmucoid variants as contributors to evasion of innate immunity and persistence within the CF lung.
Reference Key
malhotra2018mbiomixed Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Sankalp Malhotra;Dominique H. Limoli;Anthony E. English;Matthew R. Parsek;Daniel J. Wozniak;Jennifer M. Bomberger
Journal synlett
Year 2018
DOI
10.1128/mBio.00275-18
URL
http://mbio.asm.org/cgi/content/full/9/2/e00275-18
Keywords
Microbiology

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