DrrS, a small non-coding Mycobacterium tuberculosis RNA, regulates the whole genome expression shifts consistent with adaptations for survival within host macrophages

Small non-coding RNAs play a significant role in regulation of bacterial transcription and translation. Their expression in response to external factors is important for the adaptation of bacteria to changing environmental conditions. We investigated the expression of DrrS, a small noncoding RNA of Mycobacterium tuberculosis, in the mouse model in vivo, in the ex vivo model based upon infected macrophages, and in bacterial cultures, and demonstrated its significant contribution to host-pathogen interactions. Activation of the host immune system triggers NO-inducible up-regulation of DrrS in macrophage-engulfed mycobacteria. Constitutive overexpression of DrrS in cultured mycobacteria launches a broad spectrum of shifts in the bacterial transcriptome profile very similar to those reported for M. tuberculosis adaptation to hostile intra-macrophage environment, and providing defense against oxidative and NO stresses. In addition, we observed dramatic up-regulation of genes for the PE/PPE proteins and proteins of the ESX-1 and ESX-5 secretion systems. Taken together, our results suggest a direct involvement on this small RNA in the interplay between mycobacteria and the host immune system during infectious process.