Center for Antibiotic Resistance Research, SE-40530 Göteborg, Sweden; Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, SE-41346 Göteborg, Sweden.
Center for Antibiotic Resistance Research, SE-40530 Göteborg, Sweden; Mathematical Sciences, Chalmers University of Technology and the University of Gothenburg, SE-41296 Göteborg, Sweden.
Int J Antimicrob Agents. 2019 Dec;54(6):798-802. doi: 10.1016/j.ijantimicag.2019.09.017. Epub 2019 Oct 7.
It is important to understand the origins of antibiotic resistance genes so that risks associated with the emergence of novel resistance genes can be assessed and managed. The chromosomal ampC gene (CAV-1) of Aeromonas caviae (A. caviae) has been reported as the origin of mobile FOX cephalosporinases. The recent identification of A. caviae as the origin of MOX-2 cephalosporinases and the comparably great sequence divergence between FOX and MOX genes makes it unlikely that both genes arose from the same species. Therefore, this study investigated the origin of FOX cephalosporinases using large-scale genomics.
Publicly available genomes and plasmids were searched for FOX-like genes. Synteny and nucleotide identities of the identified FOX-like genes and their genetic environments were compared and a phylogenetic tree was generated.
FOX-like genes were identified in > 230 Aeromonas genomes and in 46 Enterobacteriaceae isolates. Analysis of the genomic context of CAV-1 revealed a truncated insertion sequence directly upstream of the ampC gene. The chromosomal ampCs of A. caviae (n = 31) were 75-78% identical to CAV-1. In contrast, CAV-1, mobile FOX genes and their context were 95-98% similar to the chromosomal ampC-locus of Aeromonas allosaccharophila (A. allosaccharophila) (n = 6). The A. allosaccharophila ampCs formed a monophyletic branch with mobile FOX genes, whereas the A. caviae ampCs clustered with mobile MOX genes.
These findings show that FOX cephalosporinases originate not in A. caviae, as previously reported, but in A. allosaccharophila, which is a fish pathogen. This finding agrees with the hypothesis that antibiotic use in aquaculture could have contributed to the emergence of FOX genes in human pathogens.
了解抗生素耐药基因的起源非常重要，这样可以评估和管理新出现的耐药基因相关的风险。已报道气单胞菌属（Aeromonas）的弯曲菌属（A. caviae）的染色体 ampC 基因（CAV-1）是移动 FOX 头孢菌素酶的起源。最近发现 A. caviae 是 MOX-2 头孢菌素酶的起源，而 FOX 和 MOX 基因之间的序列差异较大，这使得这两个基因不太可能来自同一物种。因此，本研究使用大规模基因组学研究了 FOX 头孢菌素酶的起源。
搜索了公开的基因组和质粒，以寻找 FOX 样基因。比较了鉴定出的 FOX 样基因及其遗传环境的同线性和核苷酸同一性，并生成了系统发育树。
在超过 230 个气单胞菌基因组和 46 个肠杆菌科分离株中鉴定出 FOX 样基因。CAV-1 基因组环境分析显示，ampC 基因上游有一个截断的插入序列。A. caviae（n=31）的染色体 ampC 与 CAV-1 有 75-78%的同一性。相比之下，CAV-1、移动 FOX 基因及其环境与嗜水气单胞菌（A. allosaccharophila）（n=6）的染色体 ampC 基因座有 95-98%的相似性。A. allosaccharophila 的 ampC 基因与移动 FOX 基因形成一个单系分支，而 A. caviae 的 ampC 基因与移动 MOX 基因聚类。
这些发现表明，FOX 头孢菌素酶不是如先前报道的那样起源于 A. caviae，而是起源于鱼类病原体嗜水气单胞菌属（A. allosaccharophila）。这一发现与抗生素在水产养殖中的使用可能导致人类病原体中 FOX 基因出现的假说一致。
