Inhibiting the stringent response blocks Mycobacterium tuberculosis entry into quiescence and reduces persistence.

ABSTRACT: The stringent response enables Mycobacterium tuberculosis (Mtb) to shut down its replication and metabolism under various stresses. Here we show that Mtb lacking the stringent response enzyme Rel_Mtb was unable to slow its replication rate during nutrient starvation. Metabolomics analysis revealed that the nutrient-starved rel_Mtb -deficient strain had increased metabolism similar to that of exponentially growing wild-type bacteria in nutrient-rich broth, consistent with an inability to enter quiescence. Deficiency of rel_Mtb increased the susceptibility of mutant bacteria to killing by isoniazid during nutrient starvation and in the lungs of chronically infected mice. We screened a pharmaceutical library of over 2 million co

SUBMITTER: Dutta NK 

PROVIDER: S-EPMC6426458 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature