Abstract：
Whole genome sequencing (WGS) of Mycobacterium avium complex (MAC) isolates in the clinical laboratory setting allows for rapid and reliable subspecies identification of a closely related complex of human pathogens. We developed a bioinformatics pipeline for accurate subspecies identification and tested 74 clinical MAC isolates from various anatomical sites. We demonstrate that reliable subspecies level identification of these common and clinically significant MAC isolates, including M. avium subsp. hominissuis (most dominant in causing lower respiratory tract infections in our cohort), M. avium subsp. avium, M. intracellulare subsp. intracellulare, and M. intracellulare subsp. chimaera, can be achieved by analysis of only two marker genes (rpoB and groEL/hsp65). We then explored the relationship between these subspecies and anatomical site of infection. Further, we conducted an in silico analysis and showed our algorithm also performed well for M. avium subsp. paratuberculosis but failed to consistently identify M. avium subsp. silvaticum and M. intracellulare subsp. yongonense, likely due to a lack of available reference genome sequences; all the 3 subspecies were not found in our clinical isolates and rarely reported to cause human infections. Accurate MAC subspecies identification may provide the tool and opportunity for better understanding of the disease-subspecies dynamics in MAC infections.
摘要：
在临床实验室环境中，鸟分枝杆菌复合物（MAC）分离株的全基因组测序（WGS）可以快速可靠地鉴定密切相关的人类病原体复合物。我们开发了用于精确亚种鉴定的生物信息学管道，并测试了来自各种解剖部位的74种临床MAC分离株。我们证明了这些常见和临床上重要的MAC分离株的可靠亚种水平鉴定，包括M.avium亚种。人类问题（在我们的队列中最主要的是引起下呼吸道感染），M.avium亚科。avium,M.细胞内亚种。细胞内，和M.胞内亚种。Chimaera,可以通过仅分析两个标记基因(rpoB和groEL/hsp65)来实现。然后，我们探索了这些亚种与感染解剖部位之间的关系。Further,我们进行了计算机模拟分析，并显示我们的算法对M.aviumsubsp也表现良好。副结核，但未能一致鉴定鸟分枝杆菌亚种。硅藻和胞内分枝杆菌亚种。yongonense,可能是由于缺乏可用的参考基因组序列;在我们的临床分离株中没有发现所有3个亚种，并且很少报告引起人类感染。准确的MAC亚种识别可能为更好地了解MAC感染中的疾病亚种动态提供工具和机会。
