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In vitro and in vivo fitness costs associated with Mycobacterium tuberculosis RpoB mutation H526D.
- Source :
-
Future microbiology [Future Microbiol] 2017 Jul; Vol. 12, pp. 753-765. Date of Electronic Publication: 2017 Mar 27. - Publication Year :
- 2017
-
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.<br />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.<br />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.
- Subjects :
- Animals
Antitubercular Agents pharmacology
Disease Models, Animal
Drug Resistance, Bacterial genetics
Genetic Complementation Test
Humans
Inflammation
Lung microbiology
Mice
Microbial Sensitivity Tests
Microbial Viability drug effects
Mycobacterium tuberculosis drug effects
Mycobacterium tuberculosis growth & development
Mycobacterium tuberculosis pathogenicity
Oxygen
Real-Time Polymerase Chain Reaction
Tuberculosis, Multidrug-Resistant microbiology
Virulence
Bacterial Proteins genetics
DNA-Directed RNA Polymerases genetics
Genetic Fitness
Mutation
Mycobacterium tuberculosis genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1746-0921
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Future microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 28343421
- Full Text :
- https://doi.org/10.2217/fmb-2017-0022