The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Genome Med. 2021 Jun 7;13(1):79. doi: 10.1186/s13073-021-00893-z.
Antimicrobial-resistant bacteria and their antimicrobial resistance (AMR) genes can spread by hitchhiking in human guts. International travel can exacerbate this public health threat when travelers acquire AMR genes endemic to their destinations and bring them back to their home countries. Prior studies have demonstrated travel-related acquisition of specific opportunistic pathogens and AMR genes, but the extent and magnitude of travel's effects on the gut resistome remain largely unknown.
Using whole metagenomic shotgun sequencing, functional metagenomics, and Dirichlet multinomial mixture models, we investigated the abundance, diversity, function, resistome architecture, and context of AMR genes in the fecal microbiomes of 190 Dutch individuals, before and after travel to diverse international locations.
Travel markedly increased the abundance and α-diversity of AMR genes in the travelers' gut resistome, and we determined that 56 unique AMR genes showed significant acquisition following international travel. These acquisition events were biased towards AMR genes with efflux, inactivation, and target replacement resistance mechanisms. Travel-induced shaping of the gut resistome had distinct correlations with geographical destination, so individuals returning to The Netherlands from the same destination country were more likely to have similar resistome features. Finally, we identified and detailed specific acquisition events of high-risk, mobile genetic element-associated AMR genes including qnr fluoroquinolone resistance genes, bla family extended-spectrum β-lactamases, and the plasmid-borne mcr-1 colistin resistance gene.
Our results show that travel shapes the architecture of the human gut resistome and results in AMR gene acquisition against a variety of antimicrobial drug classes. These broad acquisitions highlight the putative risks that international travel poses to public health by gut resistome perturbation and the global spread of locally endemic AMR genes.
抗菌药物耐药菌及其抗菌耐药性（AMR）基因可通过搭便车在人体肠道中传播。当旅行者获得其目的地特有的 AMR 基因并将其带回本国时，国际旅行会加剧这种对公共健康的威胁。先前的研究已经证明了与旅行相关的特定机会性病原体和 AMR 基因的获得，但旅行对肠道耐药组的影响的程度和范围在很大程度上仍然未知。
使用全宏基因组鸟枪法测序、功能宏基因组学和 Dirichlet 多项分布混合模型，我们调查了 190 名荷兰个体旅行前后粪便微生物组中 AMR 基因的丰度、多样性、功能、耐药组结构和背景。
旅行显著增加了旅行者肠道耐药组中 AMR 基因的丰度和 α多样性，我们确定了 56 种独特的 AMR 基因在国际旅行后显著获得。这些获得事件偏向于具有外排、失活和靶位替换耐药机制的 AMR 基因。旅行诱导的肠道耐药组的形成与地理目的地具有明显的相关性，因此从同一目的地国家返回荷兰的个体更有可能具有相似的耐药组特征。最后，我们确定并详细描述了高风险、可移动遗传元件相关 AMR 基因的特定获得事件，包括 qnr 氟喹诺酮耐药基因、bla 家族扩展谱β-内酰胺酶和质粒携带的 mcr-1 粘菌素耐药基因。
我们的研究结果表明，旅行塑造了人类肠道耐药组的结构，并导致了针对多种抗菌药物类别的 AMR 基因的获得。这些广泛的获得突显了国际旅行通过肠道耐药组扰动和局部地方性 AMR 基因的全球传播对公共健康构成的潜在风险。
