Table 4_Mycobacterium tuberculosis small RNAs MTS0997 and MTS1338 regulate both pathogen virulence and host immune responses.xlsx

However, their role in mycobacterial transcriptional profile regulation was characterized incompletely, and potential influence on host immune responses and the outcome of infection remained obscure. To obtain new insights in M. tuberculosis biology and TB pathogenesis we established unmarked single-knockout (KO) M. tuberculosis strains with deleted genes for MTS0997, or MTS1338, as well as the double KO strain.

These strains, their parental wild type progenitor and complemented double KO variant were explored in three experimental settings: (i) whole genome expression profiling during cultural growth, (ii) whole genome transcriptional analysis of murine bone marrow-derived macrophages activated or not with IFN-γ, and (iii) TB infection in genetically highly TB-susceptible mice. The results of our experiments indicate that deletion of MTS0997 sRNA results in a more pronounced impact on M. tuberculosis biology compared to MTS1338.