Mycobacterium tuberculosis Senses Host-Derived Carbon Monoxide during Macrophage Infection

Michael U. Shiloh, Paolo Manzanillo, Jeffery S. Cox

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Mycobacterium tuberculosis (MTB) expresses a set of genes known as the dormancy regulon in vivo. These genes are expressed in vitro in response to nitric oxide (NO) or hypoxia, conditions used to model MTB persistence in latent infection. Although NO, a macrophage product that inhibits respiration, and hypoxia are likely triggers in vivo, additional cues could activate the dormancy regulon during infection. Here, we show that MTB infection stimulates expression of heme oxygenase (HO-1) by macrophages and that the gaseous product of this enzyme, carbon monoxide (CO), activates expression of the dormancy regulon. Deletion of macrophage HO-1 reduced expression of the dormancy regulon. Furthermore, we show that the MTB DosS/DosT/DosR two-component sensory relay system is required for the response to CO. Together, these findings demonstrate that MTB senses CO during macrophage infection. CO may represent a general cue used by pathogens to sense and adapt to the host environment.

Original languageEnglish (US)
Pages (from-to)323-330
Number of pages8
JournalCell Host and Microbe
Volume3
Issue number5
DOIs
StatePublished - May 15 2008

Fingerprint

Carbon Monoxide
Regulon
Mycobacterium tuberculosis
Macrophages
Infection
Cues
Nitric Oxide
Mycobacterium Infections
Heme Oxygenase-1
Genes
Respiration
Enzymes
Hypoxia

Keywords

  • CELLBIO
  • MICROBIO
  • SIGNALING

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Mycobacterium tuberculosis Senses Host-Derived Carbon Monoxide during Macrophage Infection. / Shiloh, Michael U.; Manzanillo, Paolo; Cox, Jeffery S.

In: Cell Host and Microbe, Vol. 3, No. 5, 15.05.2008, p. 323-330.

Research output: Contribution to journalArticle

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