Sewage effluent from an Indian hospital harbors novel carbapenemases and integron-borne antibiotic resistance genes
Sewage effluent from an Indian hospital harbors novel carbapenemases and integron-borne antibiotic resistance genes
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DOI：
10.1186/s40168-019-0710-x
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发表时间：
2019-06-27
期刊：
影响因子：
15.5
通讯作者：
Larsson, D. G. Joakim
中科院分区：
文献类型：
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作者：
Marathe, Nachiket P.;Berglund, Fanny;Larsson, D. G. Joakim
背景：医院废水中含有大量个人的粪便物质，其中许多人正在接受抗生素治疗。因此，医院废水可能提供机会发现尚未在临床菌株中描述的新型碳青霉烯酶和其他抗性基因，这是合理的。因此，我们的目的是调查从印度孟买市收集的医院污水的微生物群和抗生素抗性组，特别关注鉴定新型碳青霉烯酶。结果：霰弹枪宏基因组学共发现112种不同的移动抗生素耐药基因类型，对几乎所有类别的抗生素都具有耐药性。β -内酰胺酶基因丰富，包括编码临床重要的碳青霉烯酶，如NDM、VIM、IMP、KPC和OXA-48。NDM（相对于16S rRNA基因的相对丰度为0.9%）是最常见的碳青霉烯酶基因，其次是OXA-58（相对于16S rRNA基因的相对丰度为0.84%）。在所研究的移动遗传元件中，1类整合子（相对于16S rRNA基因的相对丰度为11%）的丰度最高。不动杆菌属占16S rRNA总读取量的30%，鲍曼不动杆菌约占2.5%。对扩增的整合子基因盒进行高通量测序，鉴定出一种新的imp型（建议的IMP-81）碳青霉烯酶基因（8个aa取代）的功能变体，以及最近描述的新型抗性基因如sul4和bla（RSA1）。利用计算隐马尔可夫模型，我们在霰弹枪数据中检测到27个独特的金属β -内酰胺酶（MBL）基因，其中9个是新的B1亚类基因，1个是新的B2亚类基因，10个是新的B3亚类基因。七个新的MBL基因中有六个在大肠杆菌中表达时具有功能。结论：通过对印度医院废水的研究，我们对碳青霉烯酶的多样性有了更深入的了解。该研究还表明，医院废水中的微生物群可以作为新型耐药基因的储存库，包括以前未表征的具有进一步传播潜力的碳青霉烯酶。
Background: Hospital wastewaters contain fecal material from a large number of individuals, of which many are undergoing antibiotic therapy. It is, thus, plausible that hospital wastewaters could provide opportunities to find novel carbapenemases and other resistance genes not yet described in clinical strains. Our aim was therefore to investigate the microbiota and antibiotic resistome of hospital effluent collected from the city of Mumbai, India, with a special focus on identifying novel carbapenemases.Results: Shotgun metagenomics revealed a total of 112 different mobile antibiotic resistance gene types, conferring resistance against almost all classes of antibiotics. Beta-lactamase genes, including encoding clinically important carbapenemases, such as NDM, VIM, IMP, KPC, and OXA-48, were abundant. NDM (0.9% relative abundance to 16S rRNA genes) was the most common carbapenemase gene, followed by OXA-58 (0.84% relative abundance to 16S rRNA genes). Among the investigated mobile genetic elements, class 1 integrons (11% relative abundance to 16S rRNA genes) were the most abundant. The genus Acinetobacter accounted for as many as 30% of the total 16S rRNA reads, with A. baumannii accounting for an estimated 2.5%. High throughput sequencing of amplified integron gene cassettes identified a novel functional variant of an IMP-type (proposed IMP-81) carbapenemase gene (eight aa substitutions) along with recently described novel resistance genes like sul4 and bla(RSA1). Using a computational hidden Markov model, we detected 27 unique metallo-beta-lactamase (MBL) genes in the shotgun data, of which nine were novel subclass B1 genes, one novel subclass B2, and 10 novel subclass B3 genes. Six of the seven novel MBL genes were functional when expressed in Escherichia coli.Conclusion: By exploring hospital wastewater from India, our understanding of the diversity of carbapenemases has been extended. The study also demonstrates that the microbiota of hospital wastewater can serve as a reservoir of novel resistance genes, including previously uncharacterized carbapenemases with the potential to spread further.