High-resolution genomic surveillance elucidates a multilayered hierarchical transfer of resistance between WWTP- and human/animal-associated bacteria

• Main Authors: Břinda, K. (Author), Che, Y. (Author), Hanage, W. (Author), Xu, X. (Author), Yang, C. (Author), Yang, Y. (Author), Zhang, T. (Author)
• Format: Article
• Language: English
• Published: BioMed Central Ltd 2022
• Subjects: ampicillin; animal; Animals; Anti-Bacterial Agents; antibiotic resistance; antiinfective agent; Article; Bacteria; bacterial genome; bacterial virulence; bacterium; bacterium isolate; bacterium isolation; chloramphenicol; Citrobacter portucalensis; comparative genomics; conjugative plasmid; DNA extraction; DNA sequencing; DNA transfer; ecological niche; Escherichia coli; Escherichia dysenteriae; Escherichia flexneri; evolutionary adaptation; gene insertion sequence; genetic background; genetics; genome analysis; genomic DNA; Genomic epidemiology; genomic surveillance; genomics; Genomics; hierarchical clustering; horizontal gene transfer; Horizontal gene transfer; human; Humans; illumina sequencing; Insertion sequences; kanamycin; Klebsiella pneumoniae; klebsiella quasipneumoniae; MDR; multidrug resistant bacterium; multilayered hierarchical transfer; multilocus sequence typing; Nanopore; nanopore sequencing; nonhuman; pangenome; phylogeny; plasmid; Plasmidome; Plasmids; population genomics; prevalence; Proteus mirabilis; Raoultella ornithinolytica; Shigella flexneri; single nucleotide polymorphism; tetracycline; virulence factor; waste water management; waste water treatment plant; water management; Water Purification
• Online Access: View Fulltext in Publisher

 Background: Our interconnected world and the ability of bacteria to quickly swap antibiotic resistance genes (ARGs) make it particularly important to establish the epidemiological links of multidrug resistance (MDR) transfer between wastewater treatment plant (WWTP)- and human/animal-associated bacteria, under the One Health framework. However, evidence of ARGs exchange and potential factors that contribute to this transfer remain limited. Results: Here, by combining culture-based population genomics and genetic comparisons with publicly available datasets, we reconstructed the complete genomes of 82 multidrug-resistant isolates from WWTPs and found that most WWTP-associated isolates were genetically distinct from their closest human/animal-associated relatives currently available in the public database. Even in the minority of lineages that were closely related, WWTP-associated isolates were characterized by quite different plasmid compositions. We identified a high diversity of circular plasmids (264 in total, of which 141 were potentially novel), which served as the main source of resistance, and showed potential horizontal transfer of ARG-bearing plasmids between WWTP- and humans/animal-associated bacteria. Notably, the potentially transferred ARGs and virulence factors (VFs) with different genetic backgrounds were closely associated with flanking insertion sequences (ISs), suggesting the importance of synergy between plasmids and ISs in mediating a multilayered hierarchical transfer of MDR and potentiating the emergence of MDR-hypervirulent clones. Conclusion: Our findings advance the current efforts to establish potential epidemiological links of MDR transmission between WWTP- and human/animal-associated bacteria. Plasmids play an important role in mediating the transfer of ARGs and the IS-associated ARGs that are carried by conjugative plasmids should be prioritized to tackle the spread of resistance. [MediaObject not available: see fulltext.]. © 2022, The Author(s).