In vitro and in vivo fitness costs associated with Mycobacterium tuberculosis RpoB mutation H526D. Future Microbiol 2017 Jul;12(9):753-765
Date
03/28/2017Pubmed ID
28343421Pubmed Central ID
PMC5506874DOI
10.2217/fmb-2017-0022Scopus ID
2-s2.0-85022208645 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
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.
Author List
Rifat D, Campodónico VL, Tao J, Miller JA, Alp A, Yao Y, Karakousis PCAuthor
James Adam Miller MD, MPH Assistant Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntitubercular Agents
Bacterial Proteins
DNA-Directed RNA Polymerases
Disease Models, Animal
Drug Resistance, Bacterial
Genetic Complementation Test
Genetic Fitness
Humans
Inflammation
Lung
Mice
Microbial Sensitivity Tests
Microbial Viability
Mutation
Mycobacterium tuberculosis
Oxygen
Real-Time Polymerase Chain Reaction
Tuberculosis, Multidrug-Resistant
Virulence
