Phage Transduction is Involved in the Intergeneric Spread of Antibiotic Resistance-Associated bla CTX-M , mel, and tetM Loci in Natural Populations of Some Human and Animal Bacterial Pathogens

The horizontal genetic transfer (HGT) of antibiotic resistance genes (ARGs) mediated by species-specific bacteriophages contributes to the emergence of antibiotic-resistant strains in natural populations of human and animal bacterial pathogens posing a significant threat to global public health. However, it is unclear and needs to be determined whether polyvalent bacteriophages play any role in the intergeneric transmission of ARGs. In this study, we examined the genome sequences of 2239 bacteriophages from different sources for the presence of ARGs. The identified ARG-carrying bacteriophages were then analyzed by PHACTS, PHAST, and HostPhinder programs to determine their lifestyles, genes coding for bacterial cell lysis, recombinases, and a spectrum of their potential host species, respectively. We employed the SplitsTree, RDP4 and SimPlot software packages in recombination tests to identify HGT events of ARGs between these bacteriophages and bacteria. In our analyses, some ARG-carrying bacteriophages exhibited temperate and/or polyvalent patterns. The bootstrap values (97-100) for the SplitsTree-generated parallelograms, fit values (97-100) for splits networks, Phi P values (< 10 to 3.9 × 10 ), RDP4 P values (≤ 7.8 × 10 ), and the SimPlot results, provided strong statistical evidence for the phage transduction events of bla , mel, and tetM loci on inter-species level. These events involved several host species such as Escherichia coli, Salmonella enterica, Shigella sonnei, Streptococcus pneumoniae and Bacillus coagulans. HGT of mel loci between Erysipelothrix and Streptococcus phages were also detected. These results firmly suggest that certain bacteriophages possibly with temperate properties induce the intergeneric dissemination of bla , mel and tetM in the above species.