ABSTRACT

Global dissemination of ciprofloxacin-resistant Salmonella Kentucky has been observed over the past decades. In recent years, there have been reports of extended-spectrum β-lactamase (ESBL) producing S. Kentucky. Routine surveillance at the European Centre for Disease Prevention and Control (ECDC) detected cases with a ciprofloxacin-resistant S. Kentucky with the ESBL-gene bla _CTX-M-14b. Ensuing research identified 78 cases in 2013–2018 in eight European countries. Compared to other S. Kentucky and non-typhoidal Salmonella infections, reported to the European Surveillance System, these cases were more likely to be elderly and to present urinary-tract infections. Bayesian time-scaled phylogeny on whole genome sequences of isolates from these cases and supplementary isolates from public sequence databases was used to infer the origin and spread of this clone. We dated the origin of the bla _CTX-M-14b clone to approximately 2005 in Northern Africa, most likely in Egypt. The geographic origin predicted by the phylogenetic analysis is consistent with the patients’ travel history. Next to multiple introductions of the clone to Europe from Egypt, our analysis suggests that in some parts of Europe the clone might have formed a stable population, from which further spread has occurred. Comparative genomics indicated that the bla _CTX-M-14b gene is present on the bacterial chromosome, within the type VI secretion system region. The bla _CTX-M-14b gene is integrated downstream of the hcp1 gene, on a 2854 bp plasmid fragment containing also ISEcp1. This is the first report of a chromosomally integrated CTX-M gene in Salmonella spp. in Europe, previous studies having identified similar genes only on plasmids.

摘要

在过去的几十年中，已观察到耐环丙沙星的肯塔基州沙门氏菌的全球传播。近年来，已经出现了超广谱β内酰胺酶（ESBL）生产的报告小号。肯塔基州。欧洲疾病预防控制中心（ECDC）的例行监测发现了耐环丙沙星的S病例。带有ESBL基因bla _CTX-M-14b的肯塔基州。随后的研究确定了2013-2018年在八个欧洲国家中的78例。与其他S相比。肯塔基州和非伤寒沙门氏菌据欧洲监测系统报告，这些病例更可能是老年人，并出现尿路感染。来自这些病例的分离物和来自公共序列数据库的补充分离物的全基因组序列的贝叶斯时标系统发育被用来推断该克隆的起源和传播。我们将bla _CTX-M-14b克隆的起源追溯到大约2005年在北非，很可能在埃及。通过系统发育分析预测的地理起源与患者的出行历史一致。除了从埃及向欧洲多次引入该克隆外，我们的分析还表明，在欧洲某些地区，该克隆可能已经形成了稳定的种群，并由此进一步扩散。比较基因组学表明bla _CTX-M-14b基因存在于细菌染色体上的VI型分泌系统区域内。所述BLA _CTX-M-14B基因被整合的下游HCP1基因，在一个2854 bp的质粒片段也含有IS ECP1。这是沙门氏菌属中染色体整合的CTX-M基因的首次报道。在欧洲，以前的研究仅在质粒上鉴定出相似的基因。