Mixed communities of mucoid and non-mucoid Pseudomonas aeruginosa exhibit enhanced resistance to host antimicrobials
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Date
2017-03
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Abstract
Pseudomonas aeruginosa (P.a.) is a bacterial pathogen that causes chronic lung infections in cystic fibrosis (CF) patients. The CF lung is hyperinflammatory due to an abundance of neutrophil-derived antimicrobials, including reactive oxygen species [e.g. hydrogen peroxide (H2O2)] and antimicrobial peptides (e.g. LL-37). P.a. colonizes the CF lung by acquiring adaptive mutations. Mutation of mucA results in a mucoid phenotype due to the overproduction of the polysaccharide alginate. Mucoid isolates often revert to a nonmucoid phenotype through second mutations. Mucoid and nonmucoid strains are often isolated from the same patient sample, suggesting a selective advantage for the co-existence of these variants in the CF lung. We hypothesized that mucoid/non-mucoid P.a. may be differentially susceptible to neutrophil products, exhibiting heightened resistance to host factors in consortia. While clinical mucoid P.a. isolate (FRD1) was 10-fold more resistant to LL-37 compared to non-mucoid variants, FRD1 was also more sensitive to H2O2 compared to a non-mucoid, algT revertant. Resistance to H2O2 was dependent on catalase (katA) expression, which was likely regulated by two transcription factors, AlgT and AlgR. Extracellular release of KatA was found to be dependent on the expression of lys, which encodes an endolysin in P.a. already implicated in eDNA release. Co-cultures of mucoid/non-mucoid strains (mimicking CF lung co-isolates) exhibited greater tolerance to both H2O2 and LL-37 than mono-culture. These data provide an important rationale to study the interaction of mucoid/non-mucoid P.a. variants as contributors to CF pathology.
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Professional Biological Sciences: 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)