Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Perсhlozone Resistance in Clinical Isolates of Mycobacterium tuberculosis

Anastasia Ushtanit
ORCID logo ,
Yulia Mikhailova
,
Ludmila Krylova
,
Dmitry Grigorash
,
Marina Makarova
,
Svetlana Safonova
,
Danila Zimenkov
* ORCID logo
Version 1 : Received: 13 January 2023 / Approved: 17 January 2023 / Online: 17 January 2023 (01:24:59 CET)

A peer-reviewed article of this Preprint also exists.

Ushtanit, A.; Mikhailova, Y.; Krylova, L.; Grigorash, D.; Makarova, M.; Safonova, S.; Zimenkov, D. Perchlozone Resistance in Clinical Isolates of Mycobacterium tuberculosis. Antibiotics 2023, 12, 590. Ushtanit, A.; Mikhailova, Y.; Krylova, L.; Grigorash, D.; Makarova, M.; Safonova, S.; Zimenkov, D. Perchlozone Resistance in Clinical Isolates of Mycobacterium tuberculosis. Antibiotics 2023, 12, 590.

Abstract

The emergence of drug-resistant tuberculosis forced the development of new drugs and screnning of more effective or less toxic analogs. Mycolic acids biosynthesis is targeted by several antituberculosis drugs toped by the isoniazid being one of the most important in tuberculosis therapy. Recently, perchlozone, acting on another step in FAS-II cycle, received official approval and was included in the Russian national clinical guidelines. Using the serial dilution method on agar 7H10 plates for perchlozone and Sensititre MYCOTB microdilution plate we analyzed the phenotypic properties of primary M. tuberculosis clinical isolates and analyzed the molecular determinants of resistance to isoniazid, ethionamide and perchlozone. We found a wide variation in the MIC of perchlozone from 2 to 64 mg/L, correlating with the overall resistance profile: the MIC was higher for MDR and pre-XDR isolates. The cross-resistance between the ethionamide and the perchlozone was driven by mutations in ethA gene encoding monooxygenase responsible for activation of both drugs. Presumably susceptible to perchlozone wild-type strains had MICs ranged 2–4 mg/L, and the breakpoint estimated to be at 4 or 8 mg/L. In conclusion, susceptibility to perchlozone retained for a part of MDR strains, as does suceptibility to ethionamide, providing the possibility of therapy for such cases based on phenotypic or molecular analysis.

Keywords

tuberculosis; drug resistance; molecular determinants; perchlozone; ethionamide; isoniazid; thioacetozone

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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