Tuberculosis (TB) is a global infectious threat that is intensified by an increasing incidence of highly drug-resistant disease. Whole-genome sequencing (WGS) studies of Mycobacterium tuberculosis, the causative agent of TB, have greatly increased our understanding of this pathogen. Since the first M. tuberculosis genome was published in 1998, WGS has provided a more complete account of the genomic features that cause resistance in populations of M. tuberculosis, has helped to fill gaps in our knowledge of how both classical and new antitubercular drugs work, and has identified specific mutations that allow M. tuberculosis to escape the effects of these drugs. WGS studies have also revealed how resistance evolves both within an individual patient and within patient populations, including the important roles of de novo acquisition of resistance and clonal spread. These findings have informed decisions about which drug-resistance mutations should be included on extended diagnostic panels. From its origins as a basic science technique, WGS of M. tuberculosis is becoming part of the modern clinical microbiology laboratory, promising rapid and improved detection of drug resistance, and detailed and real-time epidemiology of TB outbreaks. We review the successes and highlight the challenges that remain in applying WGS to improve the control of drug-resistant TB through monitoring its evolution and spread, and to inform more rapid and effective diagnostic and therapeutic strategies.

中文翻译：

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使用全基因组测序提高结核分枝杆菌的耐药性：进展，希望和挑战。

结核病（TB）是一种全球性传染病威胁，高度耐药性疾病的发病率日益增加。结核分枝杆菌结核分枝杆菌的全基因组测序（WGS）研究极大地增进了我们对这种病原体的了解。自从第一个结核分枝杆菌基因组于1998年发布以来，WGS提供了更完整的导致结核分枝杆菌种群抗性的基因组特征的说明，帮助填补了我们关于传统和新型抗结核药物如何工作的知识的空白，并确定了可使结核分枝杆菌摆脱这些药物作用的特定突变。WGS的研究还揭示了抵抗力如何在个体患者和患者群体中演变，包括从头获得抗药性和克隆传播的重要作用。这些发现为扩大诊断小组应包括哪些耐药突变提供了依据。结核分枝杆菌WGS从其作为基础科学技术的起源开始，已成为现代临床微生物学实验室的一部分，有望对耐药性进行快速，改进的检测，并对结核病暴发进行详细而实时的流行病学研究。我们回顾了成功经验，并强调了应用WGS来监测耐药结核的演变和扩散，并提供更快速有效的诊断和治疗策略，以改善对耐药结核的控制。结核分枝杆菌WGS从其作为基础科学技术的起源开始，已成为现代临床微生物学实验室的一部分，有望对耐药性进行快速，改进的检测，并对结核病暴发进行详细而实时的流行病学研究。我们回顾了成功经验，并强调了应用WGS来监测耐药结核的演变和扩散，并提供更快速有效的诊断和治疗策略，以改善对耐药结核的控制。结核分枝杆菌WGS从其作为基础科学技术的起源开始，已成为现代临床微生物学实验室的一部分，有望对耐药性进行快速，改进的检测，并对结核病暴发进行详细而实时的流行病学研究。我们回顾了成功经验，并强调了应用WGS来监测耐药结核的演变和扩散，并提供更快速有效的诊断和治疗策略，以改善对耐药结核的控制。