In vitro and in vivo fitness costs associated with Mycobacterium tuberculosis RpoB mutation H526D

Published Date:

11/30/2018

Source:

Future Microbiol

Authors:

Rifat D, Campodónico VL, Tao J, Miller JA, Alp A, Yao Y, Karakousis PC

External link

Original Article

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.

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