Keen Eric C, Choi JooHee, Wallace Meghan A, Azar Michelle, Mejia-Chew Carlos R, Mehta Shail B, Bailey Thomas C, Caverly Lindsay J, Burnham Carey-Ann D, Dantas Gautam
The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
mSystems. 2021 Oct 26;6(5):e0119421. doi: 10.1128/mSystems.01194-21. Epub 2021 Oct 19.
Nontuberculous mycobacteria, including those in the Mycobacterium avium complex (MAC), constitute an increasingly urgent threat to global public health. Ubiquitous in soil and water worldwide, MAC members cause a diverse array of infections in humans and animals that are often multidrug resistant, intractable, and deadly. MAC lung disease is of particular concern and is now more prevalent than tuberculosis in many countries, including the United States. Although the clinical importance of these microorganisms continues to expand, our understanding of their genomic diversity is limited, hampering basic and translational studies alike. Here, we leveraged a unique collection of genomes to characterize MAC population structure, gene content, and within-host strain dynamics in unprecedented detail. We found that different MAC species encode distinct suites of biomedically relevant genes, including antibiotic resistance genes and virulence factors, which may influence their distinct clinical manifestations. We observed that M. avium isolates from different sources-human pulmonary infections, human disseminated infections, animals, and natural environments-are readily distinguished by their core and accessory genomes, by their patterns of horizontal gene transfer, and by numerous specific genes, including virulence factors. We identified highly similar MAC strains from distinct patients within and across two geographically distinct clinical cohorts, providing important insights into the reservoirs which seed community acquisition. We also discovered a novel MAC genomospecies in one of these cohorts. Collectively, our results provide key genomic context for these emerging pathogens and will facilitate future exploration of MAC ecology, evolution, and pathogenesis. Members of the Mycobacterium avium complex (MAC), a group of mycobacteria encompassing M. avium and its closest relatives, are omnipresent in natural environments and emerging pathogens of humans and animals. MAC infections are difficult to treat, sometimes fatal, and increasingly common. Here, we used comparative genomics to illuminate key aspects of MAC biology. We found that different MAC species and M. avium isolates from different sources encode distinct suites of clinically relevant genes, including those for virulence and antibiotic resistance. We identified highly similar MAC strains in patients from different states and decades, suggesting community acquisition from dispersed and stable reservoirs, and we discovered a novel MAC species. Our work provides valuable insight into the genomic features underlying these versatile pathogens.
非结核分枝杆菌，包括鸟分枝杆菌复合群（MAC）中的那些细菌，对全球公共卫生构成了日益紧迫的威胁。MAC成员在世界各地的土壤和水中普遍存在，可在人类和动物中引起各种各样的感染，这些感染往往具有多重耐药性、难以治疗且致命。MAC肺病尤其令人担忧，在包括美国在内的许多国家，其现在比结核病更为普遍。尽管这些微生物的临床重要性不断扩大，但我们对其基因组多样性的了解有限，这同样阻碍了基础研究和转化研究。在此，我们利用一组独特的基因组以前所未有的详细程度来表征MAC种群结构、基因内容和宿主内菌株动态。我们发现不同的MAC菌种编码不同的与生物医学相关的基因组合，包括抗生素抗性基因和毒力因子，这可能影响它们不同的临床表现。我们观察到，来自不同来源——人类肺部感染、人类播散性感染、动物和自然环境——的鸟分枝杆菌分离株，通过其核心基因组和辅助基因组、水平基因转移模式以及众多特定基因（包括毒力因子）很容易区分开来。我们在两个地理位置不同的临床队列内部和之间的不同患者中鉴定出高度相似的MAC菌株，这为引发社区感染的储存库提供了重要见解。我们还在其中一个队列中发现了一种新的MAC基因组种。总体而言，我们的结果为这些新兴病原体提供了关键的基因组背景，并将促进未来对MAC生态学、进化和发病机制的探索。鸟分枝杆菌复合群（MAC）的成员，这是一组包括鸟分枝杆菌及其近亲的分枝杆菌，在自然环境中无处不在，是人类和动物的新兴病原体。MAC感染难以治疗，有时会致命，且越来越常见。在此，我们使用比较基因组学来阐明MAC生物学的关键方面。我们发现不同的MAC菌种以及来自不同来源的鸟分枝杆菌分离株编码不同的与临床相关的基因组合，包括那些与毒力和抗生素抗性相关的基因。我们在来自不同州和不同年代的患者中鉴定出高度相似的MAC菌株，这表明社区感染是从分散且稳定的储存库中获得的，并且我们发现了一种新的MAC菌种。我们的工作为这些多面性病原体的基因组特征提供了有价值的见解。
