Rv1894c Is a novel hypoxia-induced nitronate monooxygenase required for mycobacterium tuberculosis virulence

Lee G. Klinkenberg, Petros C. Karakousis

Research output: Contribution to journalArticlepeer-review

Abstract

Tuberculosis is difficult to cure, requiring a minimum of 6 months of treatment with multiple antibiotics. Small numbers of organisms are able to tolerate the antibiotics and persist in the lungs of infected humans, but they still require some metabolic activity to survive. We studied the role of the hypoxia-induced Rv1894c gene in Mycobacterium tuberculosis virulence in guinea pigs, which develop hypoxic, necrotic granulomas histologically resembling those in humans and found this gene to be necessary for full bacillary growth and survival. We characterized the function of the encoded enzyme as a nitronate monooxygenase, which is needed to prevent the buildup of toxic products during hypoxic metabolism and is negatively regulated by the transcriptional repressor KstR. Future studies will focus on developing small-molecule inhibitors that target Rv1894c and its homologs, with the goal of killing persistent bacteria, thereby shortening the time needed to treat tuberculosis.

Original languageEnglish (US)
Pages (from-to)1525-1534
Number of pages10
JournalJournal of Infectious Diseases
Volume207
Issue number10
DOIs
StatePublished - May 15 2013

Keywords

  • 2-nitropropane dioxygenase
  • Mycobacterium tuberculosis
  • Pseudomonas aeruginosa
  • animal models
  • detoxification
  • dormancy
  • fatty acid synthesis
  • guinea pig
  • latency
  • latent tuberculosis infection
  • lipids
  • nitroalkane
  • oxidation
  • persistence
  • virulence

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Rv1894c Is a novel hypoxia-induced nitronate monooxygenase required for mycobacterium tuberculosis virulence'. Together they form a unique fingerprint.

Cite this