Journal article
Mixed Communities of Mucoid and Nonmucoid Pseudomonas aeruginosa Exhibit Enhanced Resistance to Host Antimicrobials
mBio, Vol.9(2), p.e00275-18
03/27/2018
DOI: 10.1128/mBio.00275-18
PMCID: PMC5874919
PMID: 29588399
Abstract
causes chronic pulmonary infections in patients with cystic fibrosis (CF).
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
and
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 (H
O
). 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 H
O
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
, encoding an endolysin implicated in autolysis and extracellular DNA (eDNA) release. Overall, these data provide a rationale to study interactions of
mucoid and nonmucoid variants as contributors to evasion of innate immunity and persistence within the CF lung.
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
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
communities
, as these variants can differentially shield one another from components of the host response.
Details
- Title: Subtitle
- Mixed Communities of Mucoid and Nonmucoid Pseudomonas aeruginosa Exhibit Enhanced Resistance to Host Antimicrobials
- Creators
- Sankalp Malhotra - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, USADominique H Limoli - Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth, Hanover, New Hampshire, USAAnthony E English - Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, USAMatthew R Parsek - Department of Microbiology, University of Washington, Seattle, Washington, USADaniel J Wozniak - Department of Microbiology, The Ohio State University, Columbus, Ohio, USA
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.9(2), p.e00275-18
- DOI
- 10.1128/mBio.00275-18
- PMID
- 29588399
- PMCID
- PMC5874919
- NLM abbreviation
- mBio
- ISSN
- 2161-2129
- eISSN
- 2150-7511
- Grant note
- R01 AI097511 / NIAID NIH HHS R01 AI077628 / NIAID NIH HHS TL1 TR001069 / NCATS NIH HHS R01 AI134895 / NIAID NIH HHS
- Language
- English
- Date published
- 03/27/2018
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083286002771
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