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 language | English (US) |
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Pages (from-to) | 753-765 |
Number of pages | 13 |
Journal | Future microbiology |
Volume | 12 |
Issue number | 9 |
DOIs | |
State | Published - Jul 2017 |
Externally published | Yes |
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)