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Antimicrobial resistance continues to be a significant and growing threat to global public health, being driven by the emerging drug-resistant and multidrug-resistant strains of human and animal bacterial pathogens. While bacteriophages are generally known to be one of the vehicles of antibiotic resistance genes (ARGs), it remains largely unclear how these organisms contribute to the dissemination of the genetic loci encoding for antibiotic efflux pumps, especially those that confer multidrug resistance, in bacteria. In this study, the in-silico recombination analyses provided strong statistical evidence for bacteriophage-mediated intra-species recombination of ARGs, encoding mainly for the antibiotic efflux proteins from the MF superfamily, as well as from the ABC and RND families, in Salmonella enterica, Staphylococcus aureus, Staphylococcus suis, Pseudomonas aeruginosa, and Burkholderia pseudomallei. Events of bacteriophage-driven intrageneric recombination of some of these genes could be also elucidated among Bacillus thuringiensis, Bacillus cereus and Bacillus tropicus natural populations. Moreover, we could also reveal the patterns of intergeneric recombination, involving the MF superfamily transporter-encoding genetic loci, induced by a Mycobacterium smegmatis phage, in natural populations of Streptomyces harbinensis and Streptomyces chartreusis. The SplitsTree- (fit: 100; bootstrap values: 92.7-100; Phi p ≤ 0.2414), RDP4- (p ≤ 0.0361), and GARD-generated data strongly supported the above genetic recombination inferences in these in-silico analyses. Thus, based on this pilot study, it can be suggested that the above mode of bacteriophage-mediated recombination plays at least some role in the emergence and transmission of multidrug resistance across a fairly broad spectrum of bacterial species and genera including human pathogens., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Unraveling the trends of phage-host versus phage-phage coevolution is critical for avoiding possible undesirable outcomes from the use of phage preparations intended for therapeutic, food safety or environmental safety purposes. We aimed to investigate a phenomenon of intergeneric recombination and its trajectories across the natural populations of phages predominantly linked to foodborne pathogens. The results from the recombination analyses, using a large array of the recombination detection algorithms imbedded in SplitsTree, RDP4, and Simplot software packages, provided strong evidence (fit: 100; P  ≤ 0.014) for both bi- and multi-directional intergeneric recombination of the genetic loci involved collectively in phage morphogenesis, host specificity, virulence, replication, and persistence. Intergeneric recombination was determined to occur not only among conspecifics of the virulent versus temperate phages but also between the phages with these different lifestyles. The recombining polyvalent phages were suggested to interact with fairly large host species networks, including sometimes genetically very distinct species, such as e.g., Salmonella enterica and/or Escherichia coli versus Staphylococcus aureus or Yersinia pestis. Further studies are needed to understand whether phage-driven intergeneric recombination can lead to undesirable changes of intestinal and other microbiota in humans and animals.

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 -17 to 3.9 × 10 -16 ), RDP4 P values (≤ 7.8 × 10 -03 ), and the SimPlot results, provided strong statistical evidence for the phage transduction events of bla CTX-M , 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 CTX-M , mel and tetM in the above species.