Title | Identification of Mycobacterium avium genes associated with resistance to host antimicrobial peptides. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Motamedi, N, Danelishvili, L, Bermudez, LE |
Journal | J Med Microbiol |
Volume | 63 |
Issue | Pt 7 |
Pagination | 923-930 |
Date Published | 2014 Jul |
ISSN | 1473-5644 |
Keywords | Animals, Antimicrobial Cationic Peptides, Cloning, Molecular, Drug Resistance, Bacterial, Gene Expression Regulation, Bacterial, Macrophages, Mice, Microbial Sensitivity Tests, Mutation, Mycobacterium avium |
Abstract |
Antimicrobial peptides are an important component of the innate immune defence. Mycobacterium avium subsp. hominissuis (M. avium) is an organism that establishes contact with the respiratory and gastrointestinal mucosa as a necessary step for infection. M. avium is resistant to high concentrations of polymyxin B, a surrogate for antimicrobial peptides. To determine gene-encoding proteins that are associated with this resistance, we screened a transposon library of M. avium strain 104 for susceptibility to polymyxin B. Ten susceptible mutants were identified and the inactivated genes sequenced. The great majority of the genes were related to cell wall synthesis and permeability. The mutants were then examined for their ability to enter macrophages and to survive macrophage killing. Three clones among the mutants had impaired uptake by macrophages compared with the WT strain, and all ten clones were attenuated in macrophages. The mutants were also shown to be susceptible to cathelicidin (LL-37), in contrast to the WT bacterium. All but one of the mutants were significantly attenuated in mice. In conclusion, this study indicated that the M. avium envelope is the primary defence against host antimicrobial peptides.
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DOI | 10.1099/jmm.0.072744-0 |
Alternate Journal | J Med Microbiol |
PubMed ID | 24836414 |
PubMed Central ID | PMC4064352 |
Grant List | R01 AI043199 / AI / NIAID NIH HHS / United States AI 043199 / AI / NIAID NIH HHS / United States |