**7. Virulent factors of** *S. Kentucky* **ST198 that may potentiate phage-mediated transduction of ARGs**

*Salmonella Kentucky* ST198 is a global contaminant and an emerging risk for foodborne illness, although first identified in Egypt it has now been isolated in several countries across the different regions in Africa [5, 49], with reservoirs in various animals and food [49–54]. Successes have been recorded with the institution of phages in controlling the spread of MDR *Salmonella Kentucky* [9, 55]; these findings however rarely discuss the tendencies of phage-host mediated propagation of ARGs or other MDR determinants. *S. Kentucky* ST198 belongs to a single lineage, which is predicted to emerged circa 1989 following the acquisition of the AMRassociated *Salmonella* genomic island (SGI) 1 (variant SGI1-K), that confers resistance to ampicillin, streptomycin, gentamicin, sulfamethoxazole and tetracycline [56]. This MDR *Salmonella Kentucky* clone has undergone substitution mutations in the quinolone-resistance-determining regions (QRDRs) of DNA gyrase (gyrA) and DNA topoisomerase IV (parC) genes, such that most strains carry three QRDR mutations which together confer resistance to ciprofloxacin. Its molecular characterization further shows a chromosomal genomic island carrying resistance genes that confer resistance to β-lactam antibiotics, carbapenems, quinolones, aminoglycosides, co-trimoxazole (trimethoprim-sulfamethoxazole), and to Azithromycin. Extended-spectrum cephalosporins (ESCs) resistance has also been associated with *S. Kentucky* ST198 [57–60]. Genetic basis for this resistance showed an extendedspectrum b-lactamase (ESBL) [61]. The aforementioned resistant properties evidently can allow for the transfer of native kanamycin resistance plasmid to strains of *S. Typhimurium* or other *Salmonella serovar* by generalized transduction as treatment with these antibiotics as reported by [38] can induce *Salmonella* phage DT104 and DT102 transmission of a native kanamycin resistance plasmid and other ARGs between serovars of *Salmonella* by generalized transduction. *S. Kentucky* also exhibits an extensive MDR pattern with diverse resistance profile cutting across human, environmental and poultry micro biomes [57]. A penta-resistant profile (SSuTCipNa) was observed in *S. Kentucky* from human, environmental and poultry samples with a deca-resistant profile, ACKSSuSxTAmcCipNa in poultry [57, 58]. *Salmonella* Phages ES18, PDT17, DT104, DT120 and other P22-like prophages like ST104 or PDT17 haboured within DT104 have been proven to be participatory in the transduction and co-transduction of genes for ACSSuT resistance phenotype [33], making *S. Kentucky* ST198 a luxurious menu for the transduction of these genes complemented by other factors that may helps in phage-mediated transduction of ARGs between serovars of *Salmonella* and other enterobacteriaceae. Several conjugative plasmids have also been detected in *S. Kentucky* ST198; IncA/C conjugative plasmids have been isolated in *S. Kentucky* ST198 that contain up to 10 ARGs for more than five classes of antibiotics. The most common ARGs carried by IncA/C are *str*AB (aminoglycosides), *sul*2 (sulfonamides), *tet*AR (tetracycline),

*Challenges of Phage Therapy as a Strategic Tool for the Control of* Salmonella Kentucky*… DOI: http://dx.doi.org/10.5772/intechopen.95329*

*bla*CMY-2 (β-lactams), *floR* (chloramphenicols) and *bla*CTX-M-25 (cephalosporin). Other genes for resistance to aminoglycosides, tetracyclines, trimethoprim, chloramphenicols, and have also been identified [49, 62–64]. *S*. *Kentucky* ST198 also contains an IncF plasmid [65]. IncF plasmids can carry multiple types of replicon associated genes, such as FIA, FII, or FIB [66]. IncF plasmids have been observed to contain ARGs, exhibiting resistance to fluoroquinolone [67], they have also been associated with *str*AB, *tet*A, *tet*C, *tet*D, *aph*A (aminoglycosides), and *sul*2 (sulphonamides) resistance [68, 69]. Another plasmid of importance carried by *S. Kentucky* ST198 is the IncHI plasmid and has been associated with *qnr* genes (fluoroquinolones) and ESBL genes [70]. The integration of one of more of these conjugative plasmids that may be in close proximity to P22-like prophages would facilitate their packaging into the core of the assembling phage during induction from its host, thus contributing to the spread of antibiotic resistance between generic and non-generic bacteria in the intestinal flora of livestock and human and in the environment causing foodborne illnesses and outbreaks. Although the mode of acquisition of Plasmids ARGSs in *Salmonella* may seem random, their proliferation in a population is usually not random. Consequently, surveillance is a necessary tool, not just for *Salmonella* and other important human and animal pathogens, but for the plasmids they carry. Therefore, the tracking of plasmids and the genes they carry would allow for a better understanding of co-selection of ARGs and the associations of plasmids with *Salmonella* serotypes [71]. Finally since *Salmonellae* phages can bind to several protein receptors in *Salmonellae* and other members of the enterobacteriaceae family thereby permitting cross-serovar and inter-specie transduction of ARGs [43], it has become necessary that measures or protocols that can hinder such developments be adopted in order to forestall the spread of *Salmonellae* associated foodborne outbreaks.

### **8. Conclusion**

The renewed and profound interest in phage therapy as a non-antibiotic measure for combating MDR strains of *Salmonellae* is a testament to their efficacy, but clearly *Salmonella Kentucky* ST198 posse's virulent factors that can potentiate phage-mediated cross-serovar transduction and co-transduction of ARGs and MDR determinants, therefore investigative laboratory protocol should therefore be sought to identify these determinants prior to the institution of phages in the treatment of non-repressive salmonellosis.

### **Conflict of interest**

Author declares none.

*Bacteriophages in Therapeutics*
