TitleIdentification of Mycobacterium avium genes associated with resistance to host antimicrobial peptides.
Publication TypeJournal Article
Year of Publication2014
AuthorsMotamedi, N, Danelishvili, L, Bermudez, LE
JournalJ Med Microbiol
IssuePt 7
Date Published2014 Jul
KeywordsAnimals, Antimicrobial Cationic Peptides, Cloning, Molecular, Drug Resistance, Bacterial, Gene Expression Regulation, Bacterial, Macrophages, Mice, Microbial Sensitivity Tests, Mutation, Mycobacterium avium

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.

Alternate JournalJ Med Microbiol
PubMed ID24836414
PubMed Central IDPMC4064352
Grant ListR01 AI043199 / AI / NIAID NIH HHS / United States
AI 043199 / AI / NIAID NIH HHS / United States