Characterization of G-Quadruplex Motifs in espB, espK, and cyp51 Genes of Mycobacterium tuberculosis as Potential Drug Targets

Mishra, Subodh Kumar; Shankar, Uma; Jain, Neha; Sikri, Kriti; Tyagi, Jaya Sivaswami; Sharma, Tarun Kumar; Mergny, Jean-Louis; Kumar, Amit

In conclusion, the current study has identified and confirmed the presence of highly conserved G4 motifs in virulence determining genes of M. tuberculosis. Moreover, the presence of these PGQs in other Mycobacterium species suggests their conserved role in the survival and virulence of bacteria, and allows us to propose them as a suitable therapeutic target for inhibiting the bacterial pathogenicity. The presence of GQs was confirmed using various biophysical approaches in the presence of a G4 stabilizing agent, TMPyP4. Lastly, the inhibitory role of GQs in the expression of espK and espB virulence genes and in the survival of M. tuberculosis was demonstrated. TMPyP4 can inhibit intracellular transcription of the G4-containing genes. Taking together all the results, this study demonstrates that the G4s in the espK and espB genes can be considered as novel targets for the development of anti-tuberculosis compounds.