In vivo transfer and microevolution of avian native IncA/C2 blaNDM-1-carrying plasmid pRH-1238 during a broiler chicken infection study [PublishAheadOfPrint]

The emergence and spread of carbapenemase-producing Enterobacteriaceae (CPE) in wildlife and livestock animals poses an important safety concern for public health. With our in vivo broiler chicken infection study we investigated transfer and experimental microevolution of the bla_NDM-1-carrying IncA/C₂ plasmid (pRH-1238) introduced by avian native Salmonella (S.) Corvallis, without inducing antibiotic selection pressure. We evaluated dependency of the time point of inoculation on donor [S. Corvallis (12-SA01738)] and a plasmid-free Salmonella spp. recipient [S. Paratyphi B (dTa+), 13-SA01617] excretion by quantifying their excretion dynamics. Using S1-PFGE plasmid profiling we gained insight into the variability of native plasmid content among S. Corvallis reisolates as well plasmid acquisition in S. Paratyphi B (dTa+) and enterobacterial gut microflora. Whole genome sequencing enabled us an in-depth insight into microevolution of pRH-1238 plasmid in S. Corvallis and enterobacterial recipient isolates. Our study revealed that the fecal excretion of avian native carbapenemase-producing S. Corvallis is significantly higher and not hampered by S. Paratyphi (dTa+). Acquisition of pRH-1238 in other Enterobacteriaceae and several transfer events of pRH-1238 plasmid to different E. coli sequence types and Klebsiella pneumoniae demonstrate interspecies broad-host range. Regardless of the microevolutionary structural deletions in pRH-1238, the single carbapenem resistance marker, bla_NDM-1, was maintained on pRH-1238 throughout the trial. Furthermore, we showed the importance of the gut E. coli population as vector of pRH-1238. In a potential scenario of NDM-1-producing S. Corvallis introduced into a broiler flock, the pRH-1238 plasmid can persist and spread to a broad-host range even in absence of antibiotic pressure.

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