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An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity.

TitleAn outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity.
Publication TypeJournal Article
Year of Publication2014
AuthorsDanilchanka O, Sun J, Pavlenok M, Maueröder C, Speer A, Siroy A, Marrero J, Trujillo C, Mayhew DL, Doornbos KS, Muñoz LE, Herrmann M, Ehrt S, Berens C, Niederweis M
JournalProc Natl Acad Sci U S A
Volume111
Issue18
Pagination6750-5
Date Published2014 May 06
ISSN1091-6490
KeywordsAmino Acid Sequence, Animals, Bacterial Outer Membrane Proteins, Bacterial Toxins, Cell Line, Exotoxins, Genes, Bacterial, Glycerol, HEK293 Cells, Humans, Jurkat Cells, Macrophages, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Mutation, Mycobacterium bovis, Mycobacterium tuberculosis, Phylogeny, Protein Structure, Tertiary, Recombinant Proteins, Sequence Homology, Amino Acid, Virulence
Abstract

The ability to control the timing and mode of host cell death plays a pivotal role in microbial infections. Many bacteria use toxins to kill host cells and evade immune responses. Such toxins are unknown in Mycobacterium tuberculosis. Virulent M. tuberculosis strains induce necrotic cell death in macrophages by an obscure molecular mechanism. Here we show that the M. tuberculosis protein Rv3903c (channel protein with necrosis-inducing toxin, CpnT) consists of an N-terminal channel domain that is used for uptake of nutrients across the outer membrane and a secreted toxic C-terminal domain. Infection experiments revealed that CpnT is required for survival and cytotoxicity of M. tuberculosis in macrophages. Furthermore, we demonstrate that the C-terminal domain of CpnT causes necrotic cell death in eukaryotic cells. Thus, CpnT has a dual function in uptake of nutrients and induction of host cell death by M. tuberculosis.

DOI10.1073/pnas.1400136111
Alternate JournalProc Natl Acad Sci U S A
PubMed ID24753609
PubMed Central IDPMC4020113
Grant ListR01 AI063432 / AI / NIAID NIH HHS / United States
AI074805 / AI / NIAID NIH HHS / United States
P01 AI074805 / AI / NIAID NIH HHS / United States
R01 AI083632 / AI / NIAID NIH HHS / United States
AI083632 / AI / NIAID NIH HHS / United States
R01 AI063446 / AI / NIAID NIH HHS / United States
AI063446 / AI / NIAID NIH HHS / United States
AI63432 / AI / NIAID NIH HHS / United States

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