title: An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity.
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.
authors.affiliation: Departments of Microbiology and Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35294.
authors.forename: Olga
authors.initials: O
authors.lastname: Danilchanka
authors.forename: Jim
authors.initials: J
authors.lastname: Sun
authors.forename: Mikhail
authors.initials: M
authors.lastname: Pavlenok
authors.forename: Christian
authors.initials: C
authors.lastname: Maueröder
authors.forename: Alexander
authors.initials: A
authors.lastname: Speer
authors.forename: Axel
authors.initials: A
authors.lastname: Siroy
authors.forename: Joeli
authors.initials: J
authors.lastname: Marrero
authors.forename: Carolina
authors.initials: C
authors.lastname: Trujillo
authors.forename: David L
authors.initials: DL
authors.lastname: Mayhew
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Doornbos
authors.forename: Luis E
authors.initials: LE
authors.lastname: Muñoz
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
authors.forename: Sabine
authors.initials: S
authors.lastname: Ehrt
authors.forename: Christian
authors.initials: C
authors.lastname: Berens
authors.forename: Michael
authors.initials: M
authors.lastname: Niederweis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005098:Exotoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005798:Genes, Bacterial; D005990:Glycerol / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D009163:Mycobacterium bovis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000633:toxicity; D017386:Sequence Homology, Amino Acid; D014774:Virulence / Q000235:genetics / Q000502:physiology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001427:Bacterial Toxins; D005098:Exotoxins; D011994:Recombinant Proteins; C000589201:Rv3903 protein, Mycobacterium tuberculosis; D005990:Glycerol
keywords: pore; secretion; transport
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