Emergence of tigecycline- and eravacycline-resistant Tet(X4)-producing Enterobacteriaceae in the gut microbiota of healthy Singaporeans

Emergence of tigecycline- and eravacycline-resistant Tet(X4)-producing Enterobacteriaceae in the gut microbiota of healthy Singaporeans
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DOI:
10.1093/jac/dkaa372
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发表时间:
2020-12-01
影响因子:
5.2
通讯作者:
Seedorf, Henning
Seedorf, Henning
中科院分区:
医学2区
文献类型:
--
作者:
Ding, Yichen;Saw, Woei-Yuh;Seedorf, Henning

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目的:最近发现的替加环素失活酶泰特(X4)可使其宿主产生高水平的替加环素耐药性,这使其成为一个公共卫生问题。本研究旨在从新加坡健康人群肠道菌群中分离和筛选泰特(X4)阳性肠杆菌科细菌。随后,对109份人类粪便样本进行了埃拉霉素耐药肠杆菌科菌株的回顾性筛选,并通过PCR进一步检测了泰特(X4)。采用16 S rRNA基因PCR和桑格测序对分离菌株进行分类鉴定。coli 2 EC 1 -1和94 EC均携带泰特(X4)基因,该基因分别由IncI 1型质粒p2 EC 1 -1和p94 EC-2编码。对109例健康人粪便标本进行回顾性筛查,结果显示产泰特(X4)肠杆菌科细菌的粪便携带率为10.1%(95% CI = 5.1%-17.3%),表明泰特(X4)广泛分布于新加坡健康个体的肠道微生物群中。据我们所知,这是第一份关于泰特(X4)在健康人群肠道微生物群中患病率的报告,也是中国以外首次描述这种耐药机制。我们的研究结果表明,在社区环境中监测泰特(X4)对于监测这种耐药机制的传播至关重要。
Objectives: The recently discovered tigecycline-inactivating enzyme Tet(X4) can confer high-Level tigecycline resistance on its hosts, which makes it a public health concern. This study focused on isolation and screening of Tet(X4)-positive Enterobacteriaceae from the gut microbiota of a cohort of healthy individuals in Singapore.Methods: MinION and Illumina sequencing was performed to obtain the complete genome sequences of Escherichia coli 2EC1-1 and 94EC. Subsequently, 109 human faecal samples were screened retrospectively for eravacycline-resistant Enterobacteriaceae strains, which were further tested for tet(X4) by PCR. The taxonomy of the isolated strains was determined by 16S rRNA gene PCR and Sanger sequencing.Results: Comparative genomic analysis of E. coli 2EC1-1 and 94EC revealed that both carry tet(X4), which is encoded by IncI1-type plasmids p2EC1-1 and p94EC-2, respectively. Retrospective screening of faecal samples collected from 109 healthy individuals showed that the faecal carriage rate of Tet(X4)-producing Enterobacteriaceae is 10.1% (95% CI = 5.1%-17.3%), suggesting that tet(X4) is widely distributed in the gut microbiota of healthy individuals in Singapore.Conclusions: To the best of our knowledge, this is the first report on the prevalence of tet(X4) in the gut microbiota of a healthy human cohort, as well as the first description of this resistance mechanism outside of China. Our findings suggest that surveillance of tet(X4) in community settings is vital to monitor the spread of this resistance mechanism.