In vitro and in vivo fitness costs associated with Mycobacterium tuberculosis RpoB mutation H526D.
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.
['Rifat|Dalin|D|', 'Campodónico|Victoria L|VL|', 'Tao|Jing|J|', 'Miller|James A|JA|', 'Alp|Alpaslan|A|', 'Yao|Yufeng|Y|', 'Karakousis|Petros C|PC|']
D000818:Animals D000995:Antitubercular Agents D001426:Bacterial Proteins D012321:DNA-Directed RNA Polymerases D004195:Disease Models, Animal D024881:Drug Resistance, Bacterial D005816:Genetic Complementation Test D056084:Genetic Fitness D006801:Humans D007249:Inflammation D008168:Lung D051379:Mice D008826:Microbial Sensitivity Tests D050296:Microbial Viability D009154:Mutation D009169:Mycobacterium tuberculosis D010100:Oxygen D060888:Real-Time Polymerase Chain Reaction D018088:Tuberculosis, Multidrug-Resistant D014774:Virulence
Mycobacterium tuberculosis rpoB progressive hypoxia nutrient starvation resuscitation-promoting factor inflammation Rpf murine model persistence stringent response virulence