In vitro and in vivo fitness costs associated with Mycobacterium tuberculosis RpoB mutation H526D
FUTURE MICROBIOLOGY, vol.12, no.9, pp.753-765, 2017 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 12 Issue: 9
- Publication Date: 2017
- Doi Number: 10.2217/fmb-2017-0022
- Journal Name: FUTURE MICROBIOLOGY
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Page Numbers: pp.753-765
- Open Archive Collection: AVESIS Open Access Collection
- Hacettepe University Affiliated: Yes
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.