Genomic epidemiology of emerging ESBL-producing <i>Salmonella</i> Kentucky <i>bla</i> <sub>CTX-M-14b</sub> in Europe
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Global dissemination of ciprofloxacin-resistant <i>Salmonella</i> Kentucky has been observed over the past decades. In recent years, there have been reports of extended-spectrum β-lactamase (ESBL) producing <i>S</i>. Kentucky. Routine surveillance at the European Centre for Disease Prevention and Control (ECDC) detected cases with a ciprofloxacin-resistant <i>S</i>. Kentucky with the ESBL-gene <i>bla</i> <sub>CTX-M-14b</sub>. Ensuing research identified 78 cases in 2013–2018 in eight European countries. Compared to other <i>S</i>. Kentucky and non-typhoidal <i>Salmonella</i> 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 <i>bla</i> <sub>CTX-M-14b</sub> 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 <i>bla</i> <sub>CTX-M-14b</sub> gene is present on the bacterial chromosome, within the type VI secretion system region. The <i>bla</i> <sub>CTX-M-14b</sub> gene is integrated downstream of the <i>hcp1</i> gene, on a 2854 bp plasmid fragment containing also IS<i>Ecp1</i>. This is the first report of a chromosomally integrated CTX-M gene in <i>Salmonella</i> spp. in Europe, previous studies having identified similar genes only on plasmids.
近数十年来，人们已观察到环丙沙星耐药的肯塔基沙门氏菌（Salmonella Kentucky）在全球范围内的传播。近年来，有研究报道了产超广谱β内酰胺酶（extended-spectrum β-lactamase, ESBL）的肯塔基沙门氏菌。欧洲疾病预防控制中心（European Centre for Disease Prevention and Control, ECDC）的常规监测发现了携带超广谱β内酰胺酶基因bla<sub>CTX-M-14b</sub>的环丙沙星耐药肯塔基沙门氏菌感染病例。后续研究于2013至2018年间在8个欧洲国家中共鉴定出78例此类病例。与欧洲监测系统上报的其他肯塔基沙门氏菌感染及非伤寒沙门氏菌（non-typhoidal Salmonella）感染病例相比，此类病例患者多为老年人，且更易表现为尿路感染。 研究人员对本次病例分离株及公共序列数据库中补充分离株的全基因组序列开展贝叶斯时间校准系统发育分析（Bayesian time-scaled phylogeny），以推断该克隆株的起源与传播路径。经分析，该携带bla<sub>CTX-M-14b</sub>基因的克隆株的起源时间可追溯至约2005年的北非地区，最可能为埃及。系统发育分析预测的地理起源与患者的旅行史相符。除该克隆株多次从埃及传入欧洲外，本研究分析还提示，在欧洲部分地区，该克隆株已形成稳定种群并发生进一步扩散。 比较基因组学分析显示，bla<sub>CTX-M-14b</sub>基因位于细菌染色体的VI型分泌系统（type VI secretion system）区域内。该基因整合于hcp1基因下游，所在的2854 bp质粒片段同时携带IS Ecp1。本研究是欧洲范围内首次在沙门氏菌属（Salmonella spp.）中报道染色体整合型CTX-M基因，既往相关研究仅在质粒上发现过此类基因。
