In vitro and in vivo fitness costs associated with Mycobacterium tuberculosis RpoB mutation H526D

Dalin Rifat, Victoria L. Campodónico, Jing Tao, James A. Miller, Alpaslan Alp, Yufeng Yao, Petros C. Karakousis

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: There is controversy regarding the potential fitness costs of rifampicin (RIF) resistance-conferring mutations in the Mycobacterium tuberculosis (Mtb) rpoB gene. We characterized the pathogenicity of an Mtb RpoB H526D mutant. Materials & methods: A mutant containing the RpoB H526D mutation was isolated from wild-type Mtb grown on RIF-containing plates and complemented for determination of in vitro and in vivo fitness costs. Results: The RpoB H526D mutant showed reduced survival relative to control strains during progressive hypoxia and delayed growth following resuscitation from nutrient starvation (p < 0.05), which was associated with reduced expression of the resuscitation-promoting factor genes rpfB, rpfC and rpfE. Relative to the isogenic wild-type strain, the mutant showed significantly attenuated growth and long-term survival as well as reduced inflammation in mouse lungs. Conclusion & future perspective: Our data suggest that RpoB H526D mutation confers a fitness cost during growth-limiting conditions in vitro and in mouse lungs.

Original languageEnglish (US)
Pages (from-to)753-765
Number of pages13
JournalFuture microbiology
Volume12
Issue number9
DOIs
StatePublished - Jul 2017

Keywords

  • Mycobacterium tuberculosis
  • Rpf
  • inflammation
  • murine model
  • nutrient starvation
  • persistence
  • progressive hypoxia
  • resuscitation-promoting factor
  • rpoB
  • stringent response
  • virulence

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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