**2. Antibiotic resistant gene**

Antibiotic resistance genes (ARGs) are an emerging public health contaminant, posing a potential global health risk. A major factor contributing to the increased environmental burden of ARGs is the rise in intensive livestock farming [13]. The World Health Organization (WHO) defines antimicrobial resistance (AMR) as "an increase in the minimum inhibitory concentration of a compound for a previously sensitive strain" [14]. Human beings consistently use large amounts of antibiotic in the human medical contexts as well as for growth factors and prophylaxis in agriculture and livestock, culminating in the contamination of environmental microbial communities. Unfortunately, even when pathogenic bacteria are the specific targets of antibiotic use, hundreds of non-pathogenic bacteria species are affected [15]. Thus, antibiotics are present in microbial communities, not only as a result of the natural lifecycle of microorganisms but also to the usage of these

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

drugs in agriculture, food industry, livestock and human health [16]. The presence of antibiotic resistance genes in environmental bacteria may be responsible for different mechanisms employed to overcome the natural antibiotics present in the environment. Recently this gene pool has been named the 'resistome', and its components can be mobilized into the microbial community affecting humans because of the participation of genetic platforms that efficiently facilitate the mobilization, transmission and maintenance of these resistance genes. Evidence for this transference has been suggested and or demonstrated using cutting-edge research techniques with newly identified widespread genes in multidrug-resistant bacteria [17]. These resistance genes include those responsible for plasmid-mediated efflux pumps conferring low-level fluoroquinolone resistance (*qepA*), ribosomal methylases affecting aminoglycosides (*armA, rtmB*) and methyltransferases affecting linezolid (*cfr*) all of which have been associated with antibiotic-producing bacteria. Recently, resistance genes whose ancestors have been identified in environmental isolates that are not recognized as antibiotic producers have also been detected. These include the *qnr* and the *blaCTX* genes compromising the activity of fluoroquinolones and extended-spectrum cephalosporins, respectively [17]. Bacteria can express antibiotic resistance through chromosomal mutations or via the acquisition of genetic material through horizontal gene transfer from other bacteria or the environment. Acquisition of genetic material via horizontal gene transfer is largely driven by mobile genetic elements (MGEs), such as plasmids, transposons or bacteriophages, which play a critical role in the evolution and ecology of bacterial communities by controlling the intra-species and interspecies exchange of genetic information [18]. While the transfer of these MGEs usually occur through transformation, transduction, or conjugation, conjugation is mostly considered the most efficient mechanism employed for the exchange of genetic material among bacteria [19]. The ease of acquisition and spread of ARGs by bacteria via conjugation is frequently through conjugative plasmids and transposons, and the contribution of these elements to antibiotic resistance pool has been extensively studied in hospital, community, agricultural and environmental settings [15–17, 20, 21], but very little is known about the role of bacteriophages as vehicles for ARGs in environmental settings. Recent findings based on cutting-edge genomic technologies suggest that, in these settings, bacteriophages play a more important role in the mobilization of ARGs than previously documented [22].

### **3. Phage transduction: primary mechanism for the transfer of ARGs**

Intensive studies of the mechanisms for horizontal gene transfer responsible for the increased spread of antibiotic resistance to foodborne bacterial pathogens have been undertaken; Conjugation, transformation, and transduction are the fundamental mechanisms by which dissemination of ARGs occurs [23]. Transduction is primarily the horizontal gene transfer mechanisms employed by most phages, and recent findings have shown phage-mediated transduction to be a significant driver in the dissemination of ARGs [24]. The concept that phage mediated transduction is a major driver of horizontal transfer of ARGs between foodborne pathogens, as well as from the environment to animals and humans, is increasingly been recognized. Phages are recognized as the most abundant organism in the biosphere, and are found in every environment regardless of their diversities, including oceans, lakes, soil, urban sewage, potable and well water, plant and animal microbial communities [25]. ARGs are often found on various MGEs, and are readily transferred horizontally by phage transduction [24]. Phages infect bacteria and either incorporate their viral genome into the host genome, replicating as part of the host (lysogenic cycle),

or replicate inside the host cell before releasing new phage particles (lytic cycle) [22, 26]. Phages can be either virulent or temperate. The mechanism of transduction has been vastly described in virulent phages (defined by their capacity to undergo lytic cycles). Following bacterial infection, there is an immediate induction of phage particles formation and lysis of the host cell but virulent phages do not integrate their DNA into the host chromosome. Temperate phages (known to undergo lysogenic cycle), integrate their DNA into the host chromosome and the prophage may remain dormant in the host until other factors like stress induces the excision of the phage from the chromosome leading to subsequent formation of phage particles and lysis of the host cell. Some phages can also adopt a pseudolysogenic state under unfavourable growth condition. In this state, their genome does not degrade but rather exist within the host cytoplasm as a plasmid and during bacterial cell division becomes incorporated into just one daughter cell [26]. Genetic materials are transferred between hosts either by generalized or specialized transduction. Virulent and temperate phages can undergo generalized transduction, here, bacterial DNA fragments are randomly packaged into the phage capsid during their lytic cycle forming a "transducing particle". These "offspring" phages do not contain phage genes, and only the capsid has a viral origin. Despite this, the transducing particle is capable of injecting the bacterial genes into a susceptible recipient cell, which can subsequently be incorporated into the host genome by recombination [5, 22, 24]. Specialized transduction is restrictive to temperate phages and results in the packaging of bacterial DNA into phages at a higher frequency; temperate phages insert their genomes into a specific region of the host chromosome. An inaccurate excision of the prophage may lead to the capture of the flanking genes adjacent to the phage integration point. If capsids carrying the rearranged phage genome with these foreign genes infect other bacteria and integrate into the host chromosome, transduction of the acquired genes will be achieved. However, the probability that the transferred genes are antibiotic resistance-related is relatively low [5].
