Transcriptomic profile of mycobacterium smegmatis in response to an imidazo[1,2-b][1,2,4,5]tetrazine reveals its possible impact on iron metabolism
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Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers Media
Abstract
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. Imidazo[1,2-b][1,2,4,5]tetrazines 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 imidazo[1,2-b][1,2,4,5]tetrazines, but
the exact mechanism of action of these compounds remains unknown. To assess
the mode of action of imidazo[1,2-b][1,2,4,5]tetrazines, 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.
Description
Keywords
Drug resistance, Drug development, Tuberculosis, Virtual screening, Bacteria
Citation
Vatlin, A. A. et al. (2021). Transcriptomic profile of mycobacterium smegmatis in response to an imidazo[1,2-b][1,2,4,5]tetrazine reveals its possible impact on iron metabolism. Frontiers in Microbiology, 12,724042 . https://doi.org/10.3389/fmicb.2021.724042