Small RNAs Mcr11 and DrrS of Mycobacterium tuberculosis as Possible Regulators of Glycerol Metabolism

The role of small non-coding RNAs Mcr11 and DrrS with its possible synergy in the metabolism of M. tuberculosis was studied. There were no noticeable differences in the growth dynamics of both strains with a single deletion of small RNAs ΔMcr11 and ΔDrrS and a strain with a double deletion ΔΔMcr11_DrrS compared to the wild-type M. tuberculosis strain during growth on standard media in vitro. However, it was found that after virulence restoration of these strains by in vivo passage through B6 mice, they showed a growth defect on Sauton’s medium with a high concentration of glycerol (6 vol %) in vitro, more pronounced in the strain with a double deletion. As it is known, growth inhibition in the presence of high concentrations of glycerol in M. tuberculosis cells was caused by the deletion of the Rv3679-3680 genes, which was due to the accumulation of the toxic metabolite methylglyoxal. According to bioinformatic predictions, the mRNA of the Rv3679 gene in the 5'-untranslated region contains two potential binding sites for the DrrS, but not for the Mcr11, suggesting that Rv3679 may be a DrrS target. The result may indicate a common regulatory activity for small RNAs DrrS and Mcr11 of M. tuberculosis with the occurrence of a synergistic effect in the development of “glycerol toxicity” in the ΔΔMcr11_DrrS strain. Thus, small RNAs Mcr11 and DrrS are involved in the regulation of M. tuberculosis glycerol metabolism pathways.