Mycobacterium tuberculosis Senses Host-Derived Carbon Monoxide during Macrophage Infection

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

Research output: Contribution to journalArticlepeer-review

179 Scopus citations


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
Issue number5
StatePublished - May 15 2008



ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology


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