DOI: 10.1101/509570Jan 2, 2019Paper

Remodeling of Mycobacterium tuberculosis lipids regulates prpCD during acid growth arrest

BioRxiv : the Preprint Server for Biology
Jacob J. Baker, Robert B. Abramovitch


Mycobacterium tuberculosis (Mtb) establishes a state of non-replicating persistence when it is cultured at acidic pH with glycerol as a sole carbon source. Growth can be restored by spontaneous mutations in the ppe51 gene or supplementation with pyruvate, supporting that acid growth arrests is a genetically controlled, adaptive process and not simply a physiological limitation associated with acidic pH. Transcriptional profiling identified the methylcitrate synthase and methylcitrate dehydratase genes ( prpC and prpD , respectively) as being selectively induced during acid growth arrest. prpCD along with isocitrate lyase ( icl ) enable Mtb to detoxify propionyl-CoA through the methylcitrate cycle. The goal of this study was to examine mechanisms underlying the regulation of prpCD during acid growth arrest. Induction of prpCD during acid growth arrest was reduced when the medium was supplemented with vitamin B12 (which enables an alternative propionate detoxification pathway) and enhanced in an icl mutant (which is required for the propionate detoxification), suggesting that Mtb is responding to elevated levels of propionyl-CoA during acidic growth arrest. We hypothesized that an endogenous source of propionyl-CoA generated duri...Continue Reading

Related Concepts

Cord Factors
Isocitrate Lyase
Metabolic Detoxication, Drug
Mycobacterium tuberculosis

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