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Title: Role of menaquinone in mycobacterial latency
Keywords: Mycobacteria; menaquinone; dormancy; BCG; Wayne model; hypoxia
Issue Date: 30-Mar-2008
Citation: LOW CARMEN (2008-03-30). Role of menaquinone in mycobacterial latency. ScholarBank@NUS Repository.
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.
Appears in Collections:Ph.D Theses (Open)

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