Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca, Mexico; Instituto de Diagnóstico y Referencia Epidemiológicos, Ciudad de México, Mexico.
Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Sinaloa, Mexico.
Infect Genet Evol. 2022 Jul;101:105288. doi: 10.1016/j.meegid.2022.105288. Epub 2022 Apr 27.
Drug resistant tuberculosis (DR-TB) is an important public health issue in different parts of the world. Mycobacterium tuberculosis complex variants (MTBC vars) preferentially infect certain hosts, limiting their distribution to different ecosystems. However, MTBC vars can infect other hosts beyond their preferred target potentially contributing to persistence of drug resistance (DR) in other niches. Here, we performed a comprehensive intra-host genetic analysis for the identification of DR-related mutations among all MTBC minor vars whole genome sequences (8,095 strains) publicly available worldwide. High confidence drug-resistance mutations in katG (isoniazid), rpsL (streptomycin), pncA (pyrazinamide), rpoB (rifampicin) and gyrA (fluoroquinolones) genes were identified among intrahost minor sub-populations in 197 different strains (2.43%) belonging to vars africanum, bovis, caprae, microti, orygis and pinnipedii. In addition, a three-dimensional structure modeling analysis to assess the role of novel mutations was also performed. Our findings highlight the importance of detecting discrete intra-host populations carrying DR mutations.
耐药结核病（DR-TB）是世界不同地区的一个重要公共卫生问题。结核分枝杆菌复合群变异株（MTBC vars）优先感染某些宿主，限制了它们在不同生态系统中的分布。然而，MTBC vars 可以感染其首选目标之外的其他宿主，从而有可能导致其他生态位中耐药性（DR）的持续存在。在这里，我们对全世界公开的所有 MTBC 次要变异株全基因组序列（8095 株）进行了全面的宿主内遗传分析，以确定与 DR 相关的突变。在 197 株不同株（2.43%）的宿主内次要亚群中，发现了 katG（异烟肼）、rpsL（链霉素）、pncA（吡嗪酰胺）、rpoB（利福平）和 gyrA（氟喹诺酮类）基因中高度可信的耐药突变，这些株属于 africanum、bovis、caprae、microti、orygis 和 pinnipedii vars。此外，还进行了三维结构建模分析，以评估新突变的作用。我们的研究结果强调了检测携带 DR 突变的离散宿主内群体的重要性。
