The transcriptional response of Mycobacterium tuberculosis to disruption of terpene nucleoside biosynthesis under normal and acid stress conditions

Comparison of Mycobacterium tuberculosis H37Rv and engineered strains that do or do not make terpene nucleosides like 1-tuberculosinyladenosine due to mutation of the gene Rv3377c, Rv3378c, both Rv3377c and Rv3378c. Bacteria were grown at pH 6.6 or pH 5.5.Terpene nucleosides account for > 1% of total lipid in Mycobacterium tuberculosis and appear to be constitutively produced despite consuming essential metabolites. Engineered mutations in the two genes essential for terpene nucleoside biosynthesis (Rv3377c, Rv3378c, both Rv3377c and Rv3378c) were compared to strains that make terpene nucleosides (H37Rv parent strain; Rv3378c mutation complemented with Rv3378c) to investigate the biological response to disruption of an abundant class of lipids. The most abundant terpene nucleoside, 1-tuberculosinyladenosine, acts as a biological weak base to facilitate growth in acidic conditions. Regulation of terpene nucleoside biosynthesis by pH was investigated by culture of bacteria at pH 6.6 and pH 5.5.