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Host cholesterol modulates the generation and enrichment of persister population during Mycobacterium tuberculosis infection.

ABSTRACT: We previously reported that the utilization of host cholesterol is essential for mycobacterial persistence. In this study, we demonstrated that cholesterol-induced activation of a ribonuclease toxin (VapC12) inhibits translation by targeting proT tRNA in Mtb. The resulting cholesterol-specific growth modulation increases the frequency of the generation of persisters in a heterogeneous Mtb population. A vapC12-null mutant strain (ΔvapC12) failed to persist and demonstrated a hypervirulent phenotype in a guinea pig model of Mtb infection. This is the first study to identify a novel strategy through which cholesterol-specific activation of a toxin–antitoxin (TA) module in Mtb enhances persister formation during infection. In addition to identifying the mechanism, the study provides opportunity for targeting persisters, a new paradigm facilitating tuberculosis drug development.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mycobacterium Tuberculosis Mycobacterium Tuberculosis M24

SUBMITTER: Renu Goel

LAB HEAD: Dr Nisheeth Agrawal

PROVIDER: PXD014323 | Pride | 2020-10-14

REPOSITORIES: Pride

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Host cholesterol modulates the generation and enrichment of persister population during Mycobacterium tuberculosis infection.

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