In vitro modeling of isoniazid resistance mechanisms in Mycobacterium tuberculosis H37Rv
نویسندگان
چکیده
Introduction Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis, has been a global threat to human beings for several decades. Treating become more difficult as prevalence drug-resistant increased globally. Evidence suggests that comprehensive landscape resistance mechanisms in MTB is ambiguous. More importantly, little known regarding series events connected before exposure anti-TB drugs, during and finally, when becomes resistant after exposure, upon analyses its genome. Methods We used wild-type strain (H37Rv) an vitro model generating induced using sub-inhibitory concentration isoniazid, generated resistance-associated variants (RAVs) were identified whole genome sequencing method. Results The detection inhA promoter mutation ( fabG1 −15C>T), which results production InhA protein, was found be major mechanism developing isoniazid first place. observed adaptation high stress by alteration abolishment KatG due katG S315N, common region confers resistance, along with K414N, N138S, A162E. Furthermore, we detected ahpC −72C>T 21C>A mutations, but further investigation needed determine their role compensating loss activity. Discussion This main where there are low levels whereas utilized mycobacterium isoniazid. Our work demonstrates this approach could provide clinically relevant information −15C>T mutation, clinical isolates. Moreover, other mutations can also These findings may shed light on impact RAV scenario under various isoniazid-pressuring conditions. research understand better mechanical within promoting promising drug prediction platform lead right treatment patients MDR-TB XDR-TB.
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ژورنال
عنوان ژورنال: Frontiers in Microbiology
سال: 2023
ISSN: ['1664-302X']
DOI: https://doi.org/10.3389/fmicb.2023.1171861