Molecular Epidemiology of Escherichia coli Producing CTX-M and pAmpC β-Lactamases from Dairy Farms Identifies a Dominant Plasmid Encoding CTX-M-32 but No Evidence for Transmission to Humans in the Same Geographical Region

Third-generation cephalosporin resistance (3GC-R) in 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 identified (131 isolates encoding CTX-M-1, -14, -15, -and 32 and the novel variant CTX-M-214), (6 isolates), and (1 isolate). A highly conserved plasmid was identified in 73 isolates, representing 27 sequence types. This novel ∼220-kb IncHI2 plasmid carrying was sequenced to closure and designated pMOO-32. It was found experimentally to be stable in cattle and human transconjugant 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 isolates we recently characterized from people living in the same geographical location, collected in parallel with farm sampling. There were close relatives of two plasmids circulating among eight human and two cattle isolates, and a closely related plasmid 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. Third-generation cephalosporins (3GCs) are critically important antibacterials, and 3GC resistance (3GC-R) threatens human health, particularly in the context of opportunistic pathogens such as There is some evidence for zoonotic transmission of 3GC-R 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 found on dairy farms in a geographically restricted region of the United Kingdom and compared these with 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 found on study farms had a significant impact on circulating 3GC-R strains or plasmids in the local human population.