Mycobacterium tuberculosis Rv2617c is involved in stress response and phage infection resistance.

Mycobacterium tuberculosis (M. tuberculosis) is the pathogen of human tuberculosis (TB). Resistance to numerous in vivo stresses, including oxidative stress, is determinant for M. tuberculosis intracellular survival, and understanding associated mechanisms is crucial for developing new therapeutic strategies. M. tuberculosis Rv2617c has been associated with oxidative stress response when interacting with other proteins in M. tuberculosis; however, its functional promiscuity and underlying molecular mechanisms remain elusive. In this study, we investigated the phenotypic changes of Mycobacterium smegmatis (M. smegmatis) expressing Rv2617c (Ms_Rv2617c) and its behavior in the presence of various in vitro stresses and phage infections. We found that Rv2617c conferred resistance to SDS and diamide while sensitizing M. smegmatis to oxidative stress (H2O2) and altered mycobacterial phenotypic properties (single-cell clone and motility), suggestive of reprogrammed mycobacterial cell wall lipid contents exemplified by increased cell wall permeability. Interestingly, we also found that Rv2617c promoted M. smegmatis resistance to infection by phages (SWU1, SWU2, D29, and TM4) and kept phage TM4 from destroying mycobacterial biofilms. Our findings provide new insights into the role of Rv2617c in resistance to oxide and acid stresses and report for the first time on its role in phage resistance in Mycobacterium.

The Gene and Regulatory Network Involved in Ethambutol Resistance in Mycobacterium tuberculosis.

Ethambutol (EMB) is used in combination with isoniazid and rifampicin for the treatment of tuberculosis caused by Mycobacterium tuberculosis. However, the incidence of EMB resistance is alarming. The EMB targets the cell wall arabinan biosynthesis. It is important to comprehensively understand the molecular basis of EMB to slow down the drug resistance rate of EMB. This study summarized the genes implicated in EMB resistance, regulatory network and the pharmacoproteomic effect of EMB in M. tuberculosis. Many of the genes related to EMB are implicated in membrane components, drug efflux, lipid metabolism, ribosome, and detoxification. The differential response model may help to design a novel anti-tuberculosis antibiotic.

Cytokine storm in tuberculosis and IL-6 involvement.

Tuberculosis is probably the most seasoned illness of the humanity. Intricacies or subsequent death emerging from these infections are frequently connected with cytokine storm. Interleukin-6 (IL-6) plays a crucial role in the immune response to tuberculosis. Therefore, there is a need to research some new therapeutic approaches to block IL-6 signaling that are right now being applied to the M. tuberculosis. In this review, we investigate the implication of IL-6 in the context of tuberculosis research.