An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity

Olga Danilchanka, Jim Sun, Mikhail Pavlenok, Christian Maueroeder, Alexander Speer, Axel Siroy, Joeli Marrero, Carolina Trujillo, David L. Mayhew, Kathryn S. Doornbos, Luis E. Munoz, Martin Herrmann, Sabine Ehrt, Christian Berens, Michael Niederweis*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

73 Citations (Web of Science)

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.
Original languageEnglish
Pages (from-to)6750-6755
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number18
DOIs
Publication statusPublished - 6 May 2014

Keywords

  • transport
  • pore
  • secretion

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