Genomic analysis reveals close genetic similarity between ESBL-producing E. coli isolates from humans and dogs, suggesting potential for inter-species transmission

Introduction: Extended-spectrum β-lactamase-(ESBL) producing
Enterobacteriaceae are emerging in hospital and community settings as
important causes of urinary tract infections. This group of
plasmid-mediated enzymes has been identified primarily in human and dog
hosts with blaCTX-M’s being most prevalent ESBLs worldwide. Our objective
was to identify horizontal gene transfer(HGT) events amongst human and
dog-derived ESBL-producing bacteria by examining genetic relatedness of
plasmid and bacterial whole genome sequences(WGS) associated with
ESBLs. By understanding genetic relatedness, we aimed to provide
insight into transmission dynamics of ESBLs and antibiotic resistance
among humans and dogs in community-acquired settings. Methods: DNA was
extracted from 16 Uropathogenic E. coli (UPEC) strains from humans to
determine plasmid sequences using Nanopore Technology. Plasmid sequences
acquired in Nanopore were used as references to collect ESBL-producing
plasmid sequences (N = 149) and WGS (N = 109) from the National Center for
Biotechnology Information (NCBI) database (accessed August 2022-July
2023). The Bacterial and Viral Bioinformatic Resource Center (BV-BRC),
Comparative Antibiotic Resistance Database (CARD), plasmid Multi-Locus
Sequence Typing (pMLST), Center for Genomic Epidemiology (CGE), and
Multi-Locus Sequence Typing (MLST) were used to analyze plasmid and whole
genome sequences. Phylogenetic analysis was also performed on plasmid and
whole genome sequences. Results: Of 149 plasmids collected from humans (n
= 125) and dogs (n = 24), 110(73.8%) were class A ESBLs with blaCTX-M-14
(32%), and blaTEM-1 (32%), predominant among the human population and
blaCTX-M-1 (31%) and blaTEM-1 (27%) among the dog population. pMLST showed
that IncF, IncI1, and IncN plasmids were the main groups contributing to
dissemination of ESBLs amongst human and dog populations. Genome
annotations revealed that plasmids carrying ESBLs harbored genes
responsible for HGT by conjugation. Neighbor-joining cluster analysis
showed human and dog-derived plasmids do share ESBL genes and other
antibiotic-resistant genes(ARGs). The maximum-likelihood tree revealed a
high predominance of ST-131 carried by E. coli serotypes O25:H4 amongst
humans and dogs. Virulence gene identification showed that UPEC strains
were not the only carriers of ESBL-producing bacteria. Discussion: Results
revealed evidence of cross-species transmission of ESBLs between humans
and dogs at plasmid and E. coli clonal levels, underscoring the need to
increase surveillance of ARGs in the community to mitigate ESBL
transmission in community settings.