AEM:中科院微生物所朱宝利课题组发表细菌耐药基因组学研究进展
2016年9月9日，美国微生物学会旗下期刊《Applied and Environmental Microbiology》杂志上在线发表了中国科学院微生物研究所朱宝利课题组在细菌耐药基因组学研究中的最新进展，研究题为The transfer network of bacterial mobile resistome connecting the animal and human microbiomes。美国微生物学会官方网站同时以Chinese investigators characterize the world of resistance gene exchange among bacteria 为题对该研究进行了新闻报道，研究被选为亮点(Spotlight)研究。胡永飞为文章第一作者，朱宝利为通讯作者。
细菌耐药是全球公共健康所面临的重要挑战。近年来，随着携带NDM-1、MCR-1等耐药基因的“超级细菌”的不断出现，细菌耐药问题日益突出。细菌具有多种耐药机制，由大量耐药基因所编码。然而，耐药基因尤其是具有高风险等级的可移动性(具有水平转移能力)的耐药基因，在细菌及人体和动物肠道菌群间的传播网络及传播驱动力并未被完全揭示。朱宝利课题组长期致力于细菌耐药基因组学研究，先后在Nature Communications、Lancet Infectious Diseases 等杂志发表系列研究工作，揭示了耐药基因在病原细菌、人体肠道菌群中的分布及传播途径和机制等。近来，课题组胡永飞等对23000余个已知细菌基因组、980万个已公布人体肠道细菌基因、测序获得的30万个养殖动物肠道细菌基因中的高风险等级可移动性耐药基因进行了全面分析。
研究发现，可移动性耐药基因主要存在于4个细菌门当中的790个细菌种之中，其丰度和转移频率在变形菌门中显著富集。这些耐药基因在细菌间的近期转移形成了一张巨大的网络，由703个细菌种、16859个种间配对所组成。对该网络进行解析，发现细菌个体间耐药基因的转移由细菌种属进化关系所主导，又同时受制于生态屏障;这一规律同样适用于耐药基因在人体和动物肠道细菌群体水平上的转移。进一步分析发现，41个人体和动物肠道菌群间相互转移的耐药基因中的33个存在于多种人体病原细菌中。该研究首次以基因组学大数据为依托，深入解析了耐药基因在细菌间的传播网络和规律，对深入认识细菌耐药性的进化、细菌耐药的形成机制等具有重要意义。
细菌耐药基因传播网络图。A：共享耐药基因的细菌种间网络；B: 细菌种间传播的耐药基因网络。
原文链接：
The transfer network of bacterial mobile resistome connecting animal and human microbiome
原文摘要：
Horizontally acquired antibiotic resistance GENEs (ARGs) in bacteria are highly mobile and have been ranked as principal risk resistance determinants. However, the transfer network of the mobile resistome and the forces driving mobile ARG transfer are largely unknown. Here, we present the whole profile of the mobile resistome in 23,425 bacterial genomes and explore the effects of phylogeny and ecology on the recent transfer (≥99% nucleotide identity) of mobile ARGs. We found that mobile ARGs are mainly present in four bacterial phyla and are significantly enriched in Proteobacteria. The recent mobile ARG transfer network, which comprises 703 bacterial species and 16,859 species pairs, is shaped by the bacterial phylogeny, while an ecological barrier also exists, especially when interrogating bacteria colonizing different human body sites. Phylogeny is still a driving force for the transfer of mobile ARGs between farm animals and the human gut, and, interestingly, the mobile ARGs that are shared between the human and animal gut microbiome are also harbored by diverse human pathogens. Together, we suggest that phylogeny and ecology are complementary in shaping the bacterial mobile resistome and exert synergistic effects on the development of antibiotic resistance in human pathogens.
作者：朱宝利
