A hydrolase of trehalose dimycolate induces nutrient influx and stress sensitivity to balance intracellular growth of Mycobacterium tuberculosis.

ABSTRACT: Chronic tuberculosis in an immunocompetent host is a consequence of the delicately balanced growth of Mycobacterium tuberculosis (Mtb) in the face of host defense mechanisms. We identify an Mtb enzyme (TdmhMtb) that hydrolyzes the mycobacterial glycolipid trehalose dimycolate and plays a critical role in balancing the intracellular growth of the pathogen. TdmhMtb is induced under nutrient-limiting conditions and remodels the Mtb envelope to increase nutrient influx but concomitantly sensitizes Mtb to stresses encountered in the host. Consistent with this, a ΔtdmhMtb mutant is more resilient to stress and grows to levels higher than those of wild-type in immunocompetent mice. By contrast, mutant growth is retarded in MyD88(-/-) mice, indicating that TdmhMtb provides a growth advantage to in

SUBMITTER: Yang Y 

PROVIDER: S-EPMC3974621 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature