Bacteriophages: from Isolation to Application

Abstract

: Bacteriophages are considered as a potential alternative to fight pathogenic bacteria during the antibiotic resistance era. With their high specificity, they are being widely used in various applications: medicine, food industry, agriculture, animal farms, biotechnology, diagnosis, etc. Many techniques have been designed by different researchers for phage isolation, purification, and amplification, each of which has strengths and weaknesses. However, all aim at having a reasonably pure phage sample that can be further characterized. Phages can be characterized based on their physiological, morphological or inactivation tests. Microscopy, in particular, has opened a wide gate not only for visualizing phage morphological structure, but also for monitoring biochemistry and behavior. Meanwhile, computational analysis of phage genomes provides more details about phage history, lifestyle, and potential for toxigenic or lysogenic conversion, which translate to safety in biocontrol and phage therapy applications. This review summarizes phage application pipelines at different levels and addresses specific restrictions and knowledge gaps in the field. Recently developed computational approaches, which are used in phage genome analysis, are critically assessed. We hope that this assessment provides researchers with useful insights for selection of suitable approaches for Phage-related research aims and applications.

Isolation and Characterization of Bacteriophage ZCSE6 against Salmonella spp.: Phage Application in Milk

“…On the other hand, the ability of phage ZCSE6 to lyse E. coli indicates that the phage can infect two different bacterial genus. Thus, phage ZCSE6 is a "divalent phage", as it has been reported before for Salmonella and E. coli phages [30,31]. Moreover, the host range of phage ZCSE6 solves one of the huge issues of antibiotics, as the narrow host range of bacteriophage reduces the risk of affecting normal microbiota and developing resistance among bacteria.…”

“…The dynamic process of isolating novel phages with complete characterization from isolation to application enriches our knowledge about the phage world. In addition, it provides information about its evolution and helps to determine the most suitable application according to its characteristics [31,49]. Nowadays, several phages that target Salmonella in foodstuff are found in the market, including PhageGuard S™ that reduces the bacteria in beef meat [50].…”

How to Train Your Phage: The Recent Efforts in Phage Training

“…Due to the massive variety in bacterial strains, it is hard to identify all the infecting bacterial strains and all their specific phages. In addition, some infections are caused by multiple bacterial strains, so it is even harder to isolate a single phage active against them all [2,103]. Therefore, deliberately expanding the phage-host range by phage training can solve these challenges in several phage applications.…”

The Synergistic Effect of Biosynthesized Silver Nanoparticles and Phage ZCSE2 as a Novel Approach to Combat Multidrug-Resistant Salmonella enterica

“…Therefore, further work is needed to test the stabilities of different biosynthesized AgNPs on different phage families. Unfortunately, low-speed centrifugation and filtration can only remove some of the bacterial debris without reducing the lipopolysaccharides (LPS), peptidoglycan, and flagella [14] in addition to the different proteins that are produced as a result of bacterial burst after phage infection. This bacterial debris could interfere with AgNPs and affect their interaction with phage.…”

“…Compared to antibiotics, phage isolation and laboratory preparation are time, effort, and cost-effective, yet further efforts are needed to transfer phage applications from laboratory bench to markets and to increase their shelf life [8][9][10]. However, the issue of bacterial resistance development towards phages could happen during the process of phage treatment [11][12][13][14]. Therefore, to improve phage efficiency, tolerance, and delivery, recent approaches support coupling phages with other bio-control agents such as antibiotics [15], natural products (e.g., venom, propolis, and extracted oils) [16], phage purified enzymes (e.g., lysins, endopeptidases, amidases, and transglycosylases) [17], in addition to syntactic compounds and nanoparticles [18][19][20].…”