Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C
Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C
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DOI：
10.1038/s41467-020-18164-7
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发表时间：
2020-09-01
影响因子：
16.6
通讯作者：
Brito, Ilana Lauren
中科院分区：
文献类型：
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作者：
Kent, Alyssa G.;Vill, Albert C.;Brito, Ilana Lauren
肠道微生物组含有抗生素耐药性（AR）基因的“沉默水库”，被认为有助于通过水平基因转移（HGT）出现多重耐药病原体。为了对抗AR的传播，最重要的是要知道哪些生物体具有移动的AR基因，哪些生物体参与HGT。尽管有表征肠道中AR基因总体丰度的方法，但短读段测序的技术限制已经排除了将细菌分类群与编码AR基因的特定移动的遗传元件（MGE）相关联。在这里，我们应用Hi-C，一种高通量，不依赖于培养的方法，来监测MGEs的细菌携带。我们比较了两个健康人和七个接受造血干细胞移植的贫血患者，他们接受了多个疗程的抗生素治疗，并且极易受到多重耐药感染的威胁。我们发现不同的HGT网络在个体之间，虽然AR和移动的基因与更多样化的类群内的血小板减少症患者比健康受试者。我们的数据进一步表明，HGT经常发生在几个星期的时间在这两个队列。虽然大多数了解AR基因传播的努力都集中在致病物种上，但我们的发现揭示了人类肠道微生物组在这一过程中的作用。将肠道微生物组中的抗生素耐药性（AR）与其细菌宿主联系起来仍然具有挑战性。在这里，作者应用细菌Hi-C绘制宏基因组中的移动的遗传元件，并说明基因存在于比健康受试者更多样化的分类群中。
The gut microbiome harbors a 'silent reservoir' of antibiotic resistance (AR) genes that is thought to contribute to the emergence of multidrug-resistant pathogens through horizontal gene transfer (HGT). To counteract the spread of AR, it is paramount to know which organisms harbor mobile AR genes and which organisms engage in HGT. Despite methods that characterize the overall abundance of AR genes in the gut, technological limitations of short-read sequencing have precluded linking bacterial taxa to specific mobile genetic elements (MGEs) encoding AR genes. Here, we apply Hi-C, a high-throughput, culture-independent method, to surveil the bacterial carriage of MGEs. We compare two healthy individuals with seven neutropenic patients undergoing hematopoietic stem cell transplantation, who receive multiple courses of antibiotics, and are acutely vulnerable to the threat of multidrug-resistant infections. We find distinct networks of HGT across individuals, though AR and mobile genes are associated with more diverse taxa within the neutropenic patients than the healthy subjects. Our data further suggest that HGT occurs frequently over a several-week period in both cohorts. Whereas most efforts to understand the spread of AR genes have focused on pathogenic species, our findings shed light on the role of the human gut microbiome in this process. Linking antibiotic resistance (AR) in the gut microbiome with their bacterial hosts remains challenging. Here, the authors apply bacterial Hi-C to map mobile genetic elements in metagenomes, and illustrate that genes are present in more diverse taxa in neutropenic patients than healthy subjects.