TitleIdentification of Mycobacterium avium pathogenicity island important for macrophage and amoeba infection.
Publication TypeJournal Article
Year of Publication2007
AuthorsDanelishvili, L, Wu, M, Stang, B, Harriff, M, Cirillo, SLG, Cirillo, S, Cirillo, JD, Cirillo, J, Bildfell, R, Arbogast, B, Bermudez, LE
JournalProc Natl Acad Sci U S A
Date Published2007 Jun 26
KeywordsAmoeba, Animals, Cell Line, Genes, Bacterial, Genome, Bacterial, Genomic Islands, Humans, Macrophages, Mutation, Mycobacterium avium, Phosphorylation, Tuberculosis

The ability to infect macrophages is a common characteristic shared among many mycobacterial species. Mycobacterium avium, Mycobacterium tuberculosis, and Mycobacterium kansasii enter macrophages, using the complement receptors CR1, CR3, CR4, and the mannose receptor. To identify M. avium genes and host cell pathways involved in the bacterial uptake by macrophages, we screened a M. avium transposon mutant library for the inability to enter macrophages. Uptake-impaired clones were selected. Sequence of six M. avium clones identified one gene involved in glycopeptidolipid biosynthesis, one gene encoding the conserved membrane protein homologue to the M. avium subsp. paratuberculosis MAP2446c gene and four others belonging to the same region of the chromosome. Analysis of the chromosome region revealed a pathogenicity island inserted between two tRNA sequences with 58% of G+C content versus 69% in the M. avium genome. The region is unique for M. avium and is not present in M. tuberculosis or M. paratuberculosis. Although the mutants did not differ from the WT bacterium regarding the binding to macrophage cell membrane, analysis of macrophage proteins after 1 h infection revealed a deficiency in the mutant to phosphorylate certain proteins on uptake. To understand M. avium interaction with two evolutionarily distinct hosts, the mutants were evaluated for Acanthamoeba castellanii invasion. The defect in the ability of the mutants to invade both cells was highly similar, suggesting that M. avium might have evolved mechanisms that are used to enter amoebas and human macrophages.

Alternate JournalProc Natl Acad Sci U S A
PubMed ID17578930
PubMed Central IDPMC1904132
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
R01 AI043199 / AI / NIAID NIH HHS / United States
AI-43199 / AI / NIAID NIH HHS / United States
P30 ES00210 / ES / NIEHS NIH HHS / United States