Genomics analysis of KPC-2 and NDM-5-producing Enterobacteriaceae in migratory birds from Qinghai Lake, China.

The study examined the epidemiological characteristics of carbapenem-resistant Enterobacteriaceae (CRE) isolated from migratory birds and surroundings in Qinghai Lake, China. We identified 69 (15.7%) CRE isolates from a total of 439 samples including 29 (6.6%) bla NDM-5 Escherichia coli and 40 (9.1%) bla KPC-2 Klebsiella pneumoniae. WGS analysis indicated that ST746, ST48, ST1011, and ST167 were the primary sequence types (ST) for bla NDM-5 E. coli, while all bla KPC-2  K. pneumoniae were ST11 and harbored numerous antibiotic resistance gene types including bla CTX-M , qnrS, and rmtB. A phylogenetic tree based on core genomes revealed that bla NDM-5 E. coli was highly heterogeneous while the bla KPC-2  K. pneumoniae was highly genetically similar within the group and to human Chinese isolates. IncX3, IncHI2, and IncFIB-HI2 plasmid replicon types were associated with bla NDM-5 spread, while IncFII-R and IncFII plasmids mediated bla KPC-2 spread. We also identified IncFII-R hybrid plasmids most likely formed by IS26-mediated integration of IncFII into IncR plasmid backbones. This also facilitated the persistence of IncFII-R plasmids and antibiotic resistance genes including bla KPC-2 . In addition, all of the bla KPC-2  K. pneumoniae isolates harbored a pLVKP-like virulence plasmid carrying a combination of two or more hypervirulence markers that included peg-344, iroB, iucA, rmpA, and rmpA2. This is the first description of ST11 K. pneumoniae that co-carried bla KPC-2 - and pLVKP-like virulence plasmids from migratory birds. The bla KPC-2  K. pneumoniae carried by migratory birds displayed high genetic relatedness to human isolates highlighting a high risk of transmission of these K. pneumoniae. KEY POINTS: • Multidrug resistance plasmids (bla KPC-2 , bla436 NDM-5 , bla  CTX-M , qnrS, and rmtB). • Co-occurrence of plasmid-mediated resistance and virulence genes. • High similarity between migratory bird genomes and humans.