印度人肠道微生物组的抗菌药耐药性负担及其产生机制

N. Chandel, Jeremiah Paul Gorremuchu, Vivek Thakur
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摘要

人体肠道微生物群中有数以百万计的细菌物种,其中包括机会性病原体,这种微生物群落会接触到食物、外部环境或药物中的抗菌剂。因此,这增加了共生菌富集耐药基因的风险,而耐药基因甚至可能在移动遗传因子的帮助下传播给机会性病原体。目前有关印度人健康肠道微生物组中耐药基因负担的信息非常有限,而印度不仅是世界上最大的肠道微生物组,而且还定期监测临床样本中抗生素耐药性的流行情况。我们分析了公开的粪便全基因组猎枪测序数据,这些数据来自三个印度健康人群的 141 份样本,目的是分析抗菌素耐药性的负担及其可能的传播模式。在所有队列中发现的总共 188 个抗菌素耐药基因中,中度到高度流行的耐药基因可能针对 7 种 "储备 "抗生素(秋水仙素、磷霉素、多粘菌素)。我们还观察到,地理位置影响了某些抗性基因的流行/丰度。与其他两个城市地区相比,部落人群中四环素和万古霉素耐药基因的含量更高,这一点很耐人寻味。大肠杆菌是耐药基因数量最多的菌种,由于它在肠道微生物组中的数量相对较少,因此有可能成为耐药基因向其他菌种横向转移的中心。最后,一部分耐药基因显示与几种类型的移动遗传因子有关,这可能会促进耐药基因在肠道群落中的传播。这是第一份关于印度多地健康肠道微生物组样本中 AMR 基因的系统性报告。虽然一些流行的 AMR 基因的趋势与全球数据相似,但一些特定人群的趋势需要决策者进一步关注。AMR 基因与移动元素的关联可能会带来向其他肠道细菌传播的风险。
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Antimicrobial resistance burden, and mechanisms of its emergence in gut microbiomes of Indian population
The human gut microbiome harbors millions of bacterial species, including opportunistic pathogens, and this microbial community is exposed to antimicrobial agents present in food, the external environment, or drugs. Thus, it increases the risk of commensals being enriched with resistant genes, which may get even transmitted to opportunistic pathogens often with the help of mobile genetic elements. There is limited information about the current burden of resistant genes in the healthy gut microbiome of the Indian population, the latter is not only the largest in the world but is also periodically monitored for the prevalence of antibiotic resistance in clinical samples.We analyzed publicly available fecal whole-metagenome shotgun sequencing data from 141 samples from three healthy Indian cohorts for antimicrobial-resistance burden, and their likely transmission modes.The overall resistance profile showed a higher number of resistance genes against tetracycline, glycopeptide, and aminoglycoside. Out of a total of 188 antimicrobial resistance genes identified in all cohorts, moderately to highly prevalent ones could potentially target seven of the ‘reserve’ group antibiotics (colistin, fosfomycin, Polymyxin). We also observed that geographical location affected the prevalence/abundance of some of the resistance genes. The higher abundance of several tetracycline and vancomycin resistance genes in tribal cohorts compared to the other two urban locations was intriguing. Species E. coli had the highest number of resistant genes, and given its relatively modest abundance in gut microbiomes can pose a risk of becoming a hub for the horizontal transfer of resistance genes to others. Lastly, a subset of the resistance genes showed association with several types of mobile genetic elements, which potentially could facilitate their transmission within the gut community.This is a first systematic report on AMR genes in healthy gut microbiome samples from multiple locations of India. While trends for several of the prevalent AMR genes showed similarity with global data, but a few population specific trends need further attention by policy-makers. The association of AMR genes with mobile elements may pose a risk for transmission to other gut bacteria.
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