Chromosomally located bla in Enterobacter cloacae complex across human-bird-environment interfaces: A one-health perspective.

To improve the understanding of antimicrobial resistance (AMR) in migratory birds derived-Enterobacter cloacae (E. cloacae) complex and its spread at the human-bird-environment interface, we isolated 11 strains of third-generation cephalosporin-resistant E. cloacae from 1003 specimens from 29 migratory bird species over two years in Chongming, Shanghai, China. The comprehensive analysis incorporated second- and third-generation sequencing techniques and extensive bioinformatic analysis. Four human-associated E. cloacae sequence types (STs), including ST432, ST412, ST1, and ST639, were found in migratory birds. We confirmed that the bla and bla genes were the major genotypes of the β-lactamase resistance genes in E. cloacae found in migratory birds. In addition, a thorough genomic analysis was performed on a global collection of 398 E. cloacae isolates carrying the bla gene from 46 different countries. China had the highest proportion with 19.10 % (76/398), followed by Singapore with 18.34 % (73/398), Nigeria with 15.83 % (63/398), and the USA with 14.07 % (56/398). The first transmission of E. cloacae carrying bla and bla was defined around 1894 and 1549, respectively. Time-based phylogenetic analysis revealed that host jumps among humans, birds, and the environment led to the emergence of modern strains with ESBL- and carbapenem-resistant genes from about 2004 to 2016. The detection rate of insertion sequences (IS) of E. cloacae carrying bla from human sources is higher than that from migratory bird sources, which is related to the different genetic environments caused by antibiotic selective pressure. It is crucial to have a comprehensive understanding of the characteristics exhibited by bla producing E. cloacae in different ecological environments. Our results contribute to the effective monitoring and implementation of proactive strategies to reduce the spread of multidrug-resistant E. cloacae.