Role of menaquinone in mycobacterial latency

Abstract

Menaquinone (MK) is abundant in mycobacteria and implicated in respiration via electron transfer reactions. MK-deficient Escherichia coli strains fail to survive in nutrient-limited anaerobic conditions. Since such conditions are encountered by intracellular mycobacteria and MTB genome contains homologues of most E. coli men genes, we hypothesised that MK-mediated metabolic processes are required for mycobacterial persistence within host cells. This project shows evidence that MK is required by active and non-replicating Mycobacterium bovis BCG using RT-PCR in the established Wayne model of latency and in mice. A BCG menA gene knock-down (KD) mutant strain generated by anti-sense strategy was attenuated in growth under oxygen-limiting conditions, in macrophages and mice. The mutant was less affected by MK analogues than controls. Active and non-replicating cultures were inhibited differentially by MK analogues in vitro and in vivo. Hence, MK could serve as an adjunct agent to conventional drugs to eliminate active and chronic tuberculosis.