Online service for interpretation of the resistance prediction results to bedaquiline by the molecular data

• Main Authors: V. V. Sinkov, I. G. Kondratov, O. B. Ogarkov, S. N. Zhdanova, A. P. Noskov, P. A. Khromova, E. A. Orlova, A. V. Labygina, L. V. Rychkova, L. I. Kolesnikova, В. В. Синьков, И. Г. Кондратов, О. Б. Огарков, С. Н. Жданова, А. П. Носков, П. А. Хромова, Е. А. Орлова, А. В. Лабыгина, Л. В. Рычкова, Л. И. Колесникова
• Other Authors: Исследование выполнено за счет гранта Российского научного фонда (проект № 23-15-00280).
• Format: Article in Journal/Newspaper
• Language: Russian
• Published: Scientific Centre for Family Health and Human Reproduction Problems 2024
• Subjects: pepQ; sequencing; resistance; genes; atpE; mmpR; mmpL5; mmpS5; Rv0678; Rv1979c; секвенирование; резистентность; гены; Yakutia; Саха; Якути*
• Online Access: https://www.actabiomedica.ru/jour/article/view/4498; https://doi.org/10.29413/ABS.2023-8.6.11

Background. Bedaquiline is a new and promising anti-tuberculosis drug, but longterm use requires resistance. This is due to mutations in the atpE and mmpR genes in M. tuberculosis (MBT).The aim of the research was to test a system for automated interpretation of results for predicting resistance to bedaquiline by the molecular data.Materials and methods. DNA was isolated from strains of M. tuberculosis in the Irkutsk region and Yakutia. The total quantity of DNA samples was 27 strains from Yakutia and 21 strains from the Irkutsk region. The study of MBT genomes was carried out on the DNA previously obtained by the authors in the territories of the Irkutsk region (n = 5), Yakutia (n = 4), Buryatia (n = 3), Zabaykalskiy kray (n = 4) and the Far East (n = 8). We used the BSATool program to detect bedaquiline resistance based on Sanger and genomic data. Sanger sequencing analyzed the atpE and mmpR genes, and whole genome sequencing examined mutations in the same sequences, as well as additionally in mmpL5, mmpS5, Rv0678, Rv1979c, and pepQ.Results. Complete agreement between the phenotypic and genotypic analysis of resistance to bedaquiline was found for three strains from Yakutia. One genome with significant mutations to bedaquiline was identified. A conclusion was made about the importance of molecular analysis of target genes with subsequent detection of resistance to bedaquiline in silico. Обоснование. Бедаквилин – новый и многообещающий противотуберкулёзный препарат, однако при длительном лечении к нему развивается устойчивость. Это связано преимущественно с мутациями в генах atpE и mmpR у M. tuberculosis (МБТ).Цель работы. Апробация системы автоматизированной интерпретации результатов при прогнозировании устойчивости к бедаквилину на основе молекулярно-биологических данных.Материалы и методы. ДНК выделяли из штаммов M. tuberculosis, циркулировавших в Иркутской области и Республике Саха (Якутии). Общее количество исследованных ДНК составило 27 штаммов из Якутии и 21 штамм из Иркутской области. Исследование ...