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.