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  • Transcriptomic Profile of M...
    Vatlin, Aleksey A.; Shitikov, Egor A.; Shahbaaz, Mohd; Bespiatykh, Dmitry A.; Klimina, Ksenia M.; Christoffels, Alan; Danilenko, Valery N.; Maslov, Dmitry A.

    Frontiers in microbiology, 08/2021, Letnik: 12
    Journal Article

    Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex bacteria, is one of the most pressing health problems. The development of new drugs and new therapeutic regimens effective against the pathogen is one of the greatest challenges in the way of tuberculosis control. Imidazo1,2- b 1,2,4,5tetrazines have shown promising activity against M. tuberculosis and M. smegmatis strains. Mutations in MSMEG_1380 lead to mmpS5–mmpL5 operon overexpression, which provides M. smegmatis with efflux-mediated resistance to imidazo1,2- b 1,2,4,5tetrazines, but the exact mechanism of action of these compounds remains unknown. To assess the mode of action of imidazo1,2- b 1,2,4,5tetrazines, we analyzed the transcriptomic response of M. smegmatis to three different concentrations of 3a compound: 1/8×, 1/4×, and 1/2× MIC. Six groups of genes responsible for siderophore synthesis and transport were upregulated in a dose-dependent manner, while virtual docking revealed proteins involved in siderophore synthesis as possible targets for 3a . Thus, we suggest that imidazo1,2- b 1,2,4,5tetrazines may affect mycobacterial iron metabolism.