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


Rifat D., Campodnico V. L. , Tao J., Miller J. A. , Alp A. , Yao Y., ...More

FUTURE MICROBIOLOGY, vol.12, no.9, pp.753-765, 2017 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 12 Issue: 9
  • Publication Date: 2017
  • Doi Number: 10.2217/fmb-2017-0022
  • Title of Journal : FUTURE MICROBIOLOGY
  • Page Numbers: pp.753-765

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.