Comparative Genomics of Mycobacterium avium Complex Reveals Signatures of Environment-Specific Adaptation and Community Acquisition.
Comparative Genomics of Mycobacterium avium Complex Reveals Signatures of Environment-Specific Adaptation and Community Acquisition.
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DOI：
10.1128/msystems.01194-21
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发表时间：
2021-10-26
期刊：
影响因子：
6.4
通讯作者：
Dantas G
中科院分区：
文献类型：
--
作者：
Keen EC;Choi J;Wallace MA;Azar M;Mejia-Chew CR;Mehta SB;Bailey TC;Caverly LJ;Burnham CD;Dantas G
非结核分枝杆菌，包括鸟分枝杆菌复合群（MAC）中的那些，对全球公共卫生构成日益紧迫的威胁。MAC成员普遍存在于世界各地的土壤和水中，在人类和动物中引起各种各样的感染，这些感染通常具有多重耐药性，难以治愈和致命。MAC肺病尤其令人担忧，目前在包括美国在内的许多国家比结核病更普遍。虽然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，阻碍了基础和转化研究。在这里，我们利用了一个独特的基因组集合，以前所未有的细节来表征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物种编码不同的生物医学相关基因，包括抗生素耐药基因和毒力因子，这可能会影响其独特的临床表现。我们观察到M.来自不同来源的禽流感病毒分离株--人类肺部感染、人类播散性感染、动物和自然环境--很容易通过它们的核心和附属基因组、通过它们的水平基因转移模式和通过许多特异性基因（包括毒力因子）来区分。我们从两个地理上不同的临床队列内和跨两个地理上不同的患者中鉴定出高度相似的MAC菌株，为种子社区获取的储库提供了重要的见解。我们还在其中一个队列中发现了一种新的MAC基因种。总的来说，我们的研究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MAC生态学，进化和发病机制的未来探索。鸟分枝杆菌复合群（MAC）是一组包括M.鸟类及其近亲在自然环境中无处不在，并成为人类和动物的新病原体。MAC感染很难治疗，有时是致命的，并且越来越常见。在这里，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物种和M。来自不同来源的禽流感病毒分离株编码不同的临床相关基因组，包括毒力和抗生素抗性基因。我们在不同州和不同年代的患者中发现了高度相似的MAC菌株，这表明社区从分散和稳定的水库中获得，我们发现了一种新的MAC物种。我们的工作提供了有价值的洞察这些多功能病原体的基因组特征。
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. IMPORTANCE 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.