Modulatory Impact of the sRNA Mcr11 in Two Clinical Isolates of Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) is a successful pathogen causing tuberculosis (TB) disease in humans. It has been shown, that some circulating strains of Mtb in TB endemic populations, are more virulent and more transmissible than others, which may be related to their evolved adaptations to modulate the host immune responses. Underlying these adaptations to the stressful conditions, different genetic regulatory networks involved sRNAs that are mostly unknown for Mtb. We have previously shown that Mcr11 is one of the main sRNAs that determine transcriptomic differences among the Colombian clinical isolates UT127 and UT205 compared to the laboratory strain H37Rv. We found that the knock-down of mcr11 using CRISPRi has a major impact on phenotypic traits, especially in the clinical isolate UT205. Through the analysis of RNA-seq during the knock-down of mcr11 in UT205, we found a downregulation of genes mainly involved in lipid synthesis, lipid metabolism, ribosomal proteins, transport systems, respiratory and energy systems, membrane and cell wall components, intermediary metabolism, lipoproteins and virulence genes. One of the most interesting genes showing transcriptomic changes is OprA (encoded by the gene rv0516c), which has been involved in the K+ regulation. Overall, our data may suggest that one of the prominent roles of the sRNA Mcr11 is to regulate genes that control Mtb growth and osmoregulation.

Automated summary

Mycobacterium tuberculosis (Mtb) is a pathogen causing tuberculosis (TB) in humans. Some circulating strains of Mtb are more virulent and transmissible than others. sRNAs, including Mcr11, play a crucial role in the adaptive response of Mtb to host immune responses. Knocking down of mcr11 leads to downregulation of genes involved in lipid synthesis, metabolism, respiratory and energy systems, membrane and cell wall components, intermediary metabolism, and virulence genes. The sRNA Mcr11 may regulate genes that control Mtb growth and osmoregulation, with OprA (encoded by the gene rv0516c) being one of the interesting genes involved.