Molecular epidemiology of Escherichia coli producing CTX-M and plasmid AmpC-type ß-lactamases from dairy farms identifies a dominant plasmid encoding CTX-M-32 but no evidence for transmission to humans in the same geographical region

Molecular epidemiology of Escherichia coli producing CTX-M and plasmid AmpC-type ß-lactamases from dairy farms identifies a dominant plasmid encoding CTX-M-32 but no evidence for transmission to humans in the same geographical region
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从奶牛场产生 CTX-M 和质粒 AmpC 型 β-内酰胺酶的大肠杆菌的分子流行病学鉴定出编码 CTX-M-32 的显性质粒,但没有证据表明在同一地理区域传播给人类

DOI:
10.1101/845917
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发表时间:
2019
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通讯作者:
Findlay J
Findlay J
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作者:
Findlay J

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大肠杆菌中的第三代头孢菌素耐药性 (3GC-R) 是人类和养殖动物群体中日益严重的问题。我们对先前从英格兰西南部奶牛场收集的 138 个代表性 3GC-R 分离株进行了全基因组测序分析,并通过 PCR 确认其携带获得的 3GC-R 基因。该分析鉴定出blaCTX-M(编码CTX-M-1、-14、-15、-和32以及新变体CTX-M-214的131个分离株)、blaCMY-2(6个分离株)和blaDHA-1(1个分离株)。在代表 27 种大肠杆菌序列类型的 73 个分离株中鉴定出高度保守的质粒。这种携带blaCTX-M-32的新型~220-kb IncHI2质粒被测序至闭合并命名为pMOO-32。实验发现,即使在没有选择压力的情况下,它在牛和人类转接合体大肠杆菌中也很稳定,并且通过多重 PCR 发现它存在于 26 个研究农场中,代表了超过 1,500 平方公里的显着传播范围。然而,在我们最近从生活在同一地理位置的人中分离出的人类尿大肠杆菌分离株中,并没有发现该质粒,这些分离株是与农场采样同时收集的。在8个人和2个牛分离株中存在两个blaCTX-M质粒的近亲,并且在1个牛和1个人分离株中发现了密切相关的blaCMY-2质粒。然而,没有发现同一地区农场和人类之间最近共享 3GC-R 菌株的系统发育证据。 重要性 第三代头孢菌素 (3GC) 是极其重要的抗菌药物,3GC 耐药性 (3GC-R) 威胁人类健康,特别是在大肠杆菌等机会性病原体的情况下。有一些证据表明 3GC-R 大肠杆菌通过食物进行人畜共患传播,但很少有人研究通过人与当地农场附近环境的相互作用进行传播的可能性。我们对在英国某个地理限制区域的奶牛场中发现的获得的 3GC-R 大肠杆菌进行了特征分析,并将其与平行收集的来自同一地区居民的大肠杆菌进行了比较。虽然有强有力的证据表明最近农场之间存在 3GC-R 菌株和质粒的传播(包括一种具有显着传播能力的流行性质粒),但没有证据表明在研究农场发现的 3GC-R 大肠杆菌对当地人群中循环的 3GC-R 大肠杆菌菌株或质粒有重大影响。
Third-generation cephalosporin resistance (3GC-R) in Escherichia coli is a rising problem in human and farmed-animal populations. We conducted whole-genome sequencing analysis of 138 representative 3GC-R isolates previously collected from dairy farms in southwest England and confirmed by PCR to carry acquired 3GC-R genes. This analysis identifiedblaCTX-M(131 isolates encoding CTX-M-1, -14, -15, -and 32 and the novel variant CTX-M-214),blaCMY-2(6 isolates), andblaDHA-1(1 isolate). A highly conserved plasmid was identified in 73 isolates, representing 27 E. coli sequence types. This novel ∼220-kb IncHI2 plasmid carryingblaCTX-M-32was sequenced to closure and designated pMOO-32. It was found experimentally to be stable in cattle and human transconjugant E. coli even in the absence of selective pressure and was found by multiplex PCR to be present on 26 study farms representing a remarkable range of transmission over 1,500 square kilometers. However, the plasmid was not found among human urinary E. coli isolates we recently characterized from people living in the same geographical location, collected in parallel with farm sampling. There were close relatives of twoblaCTX-Mplasmids circulating among eight human and two cattle isolates, and a closely relatedblaCMY-2plasmid was found in one cattle and one human isolate. However, phylogenetic evidence of recent sharing of 3GC-R strains between farms and humans in the same region was not found.IMPORTANCEThird-generation cephalosporins (3GCs) are critically important antibacterials, and 3GC resistance (3GC-R) threatens human health, particularly in the context of opportunistic pathogens such as Escherichia coli. There is some evidence for zoonotic transmission of 3GC-R E. coli through food, but little work has been done examining possible transmission via interaction of people with the local near-farm environment. We characterized acquired 3GC-R E. coli found on dairy farms in a geographically restricted region of the United Kingdom and compared these with E. coli from people living in the same region, collected in parallel. While there is strong evidence for recent farm-to-farm transmission of 3GC-R strains and plasmids—including one epidemic plasmid that has a remarkable capacity to be transmitted—there was no evidence that 3GC-R E. coli found on study farms had a significant impact on circulating 3GC-R E. coli strains or plasmids in the local human population.