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旅行者返回英国后肠道中抗生素耐药决定因素的流行率和持久性与致病性大肠杆菌的定植有关。

Prevalence and Persistence of Antibiotic Resistance Determinants in the Gut of Travelers Returning to the United Kingdom is Associated with Colonization by Pathogenic Escherichia coli.

机构信息

Gastrointestinal Bacteria Reference Unit, UK Health Security Agency London, United Kingdom.

Faculty of Veterinary Medicine, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, the Netherlands.

出版信息

Microbiol Spectr. 2023 Aug 17;11(4):e0518522. doi: 10.1128/spectrum.05185-22. Epub 2023 May 31.

DOI:10.1128/spectrum.05185-22
PMID:37255437
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10433802/
Abstract

The gut microbiota constitutes an ideal environment for the selection, exchange, and carriage of antibiotic resistance determinants (ARDs), and international travel has been identified as a risk factor for acquisition of resistant organisms. Here, we present a longitudinal metagenomic analysis of the gut resistome in travellers to "high-risk" countries (Gutback). Fifty volunteers, recruited at a travel clinic in London, United Kingdom, provided stool samples before (pre-travel), immediately after (post-travel), and 6 months after their return (follow-up) from a high-risk destination. Fecal DNA was extracted, metagenomic sequencing performed and the resistome profiled. An increase in abundance and diversity of resistome was observed after travel. Significant increases in abundance were seen in antimicrobial genes conferring resistance to macrolides, third-generation cephalosporins, aminoglycosides, and sulfonamides. There was a significant association with increased resistome abundance if the participant experienced diarrhea during travel or took antibiotics, but these two variables were co-correlated. The resistome abundance returned to pre-travel levels by the 6-month sample point but there was evidence of persistence of several ARDs. The post-travel samples had an increase in abundance Escherichia coli which was positively associated with many acquired resistant determinants. Virulence and phylogenetic profiling revealed pathogenic E. coli significantly contributed to this increase abundance. In summary, in this study, foreign travel remains a significant risk factor for acquisition of microbes conferring resistance to multiple classes of antibiotics, often associated with symptomatic exposure to diarrhoeagenic E. coli. A future where antimicrobial therapy is severely compromised by the increase in resistant organisms is of grave concern. Given the variability in prevalence and diversity of antimicrobial resistance determinants in different geographical settings, international travel is a known risk factor for acquisition of resistant organisms into the gut microbiota. In this study, we show the utility of metagenomic approaches to quantify the levels of acquisition and carriage of resistance determinants after travel to a "high-risk" setting. Significant modulation to the resistome was seen after travel that is largely resolved within 6 months, although evidence of persistence of several ARDs was observed. Risk factors for acquisition included experiencing a diarrheal episode and the use of antibiotics. Colonization by pathogenic Escherichia coli was correlated with an increase in acquisition of antimicrobial resistance determinants, and as such established public health guidance to travelers on food and water safety remain an important message to reduce the spread of antibiotic resistance.

摘要

肠道微生物群是抗生素耐药决定因素(ARD)选择、交换和传播的理想环境,国际旅行已被确定为获得耐药生物的危险因素。在这里,我们展示了一项针对前往“高风险”国家(Gutback)旅行者肠道耐药组的纵向宏基因组分析。50 名志愿者在英国伦敦的旅行诊所招募,在旅行前(旅行前)、旅行后立即(旅行后)和旅行后 6 个月(随访)提供粪便样本。提取粪便 DNA,进行宏基因组测序,并对耐药组进行分析。旅行后观察到耐药组的丰度和多样性增加。观察到对抗生素具有抗药性的抗菌基因的丰度显著增加,这些抗生素包括大环内酯类、第三代头孢菌素、氨基糖苷类和磺胺类药物。如果参与者在旅行中出现腹泻或服用抗生素,耐药组的丰度会显著增加,但这两个变量是相关的。到 6 个月的样本点时,耐药组的丰度恢复到旅行前的水平,但有证据表明几种 ARD 持续存在。旅行后的样本中大肠杆菌的丰度增加,这与许多获得的耐药决定因素呈正相关。毒力和系统发育分析显示,致病性大肠杆菌显著导致了这种丰度的增加。总之,在这项研究中,出国旅行仍然是获得对多种抗生素具有耐药性的微生物的重要危险因素,这些微生物通常与接触腹泻性大肠杆菌有关。未来,由于增加的耐药生物对抗菌治疗的严重影响,这是一个严重的问题。鉴于不同地理环境中抗菌药物耐药决定因素的流行率和多样性存在差异,国际旅行是肠道微生物群获得耐药生物的已知危险因素。在这项研究中,我们展示了宏基因组方法在定量旅行到“高风险”环境后获得和携带耐药决定因素水平方面的应用。旅行后观察到耐药组发生显著变化,6 个月内基本得到解决,但观察到几种 ARD 持续存在的证据。获得的危险因素包括出现腹泻症状和使用抗生素。致病性大肠杆菌的定植与获得抗菌药物耐药决定因素的增加相关,因此,向旅行者提供有关食物和水安全的既定公共卫生指南仍然是减少抗生素耐药传播的重要信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/586f/10433802/444c7bc0c84f/spectrum.05185-22-f005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/586f/10433802/20d1a75499e8/spectrum.05185-22-f001.jpg
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