Currently, twelve families of phage are considered for phage therapy against infectious diseases (Table 1). Thus, bacteriophages are divided into two groups: coated and uncovered. In addition, bacteriophages proliferation is similar to that of other viruses [13]. Also, bacteriophages attach to a specific receptor in the bacterial cell wall; after binding to a specific receptor in the bacterial cell wall, the phage genome enters the cell. The phage capsid coating remains on the bacterial cell wall and does not enter the bacterium. Also, after the bacteriophage enters the host cell, the phage genome is destroyed and degraded. Since then, an abundance of phages in the environment has been high. So bacteria have a mechanism to destroy the phage genome and prevent infection by these viruses. In addition, there are some loci in the phage genome; these loci are called restriction loci [14]. Therefore, bacterial enzymes can identify these areas and cut the phage genome in these areas. So, after phage genome cleavage, phage DNA is destroyed by bacterial enzymes. Also, as a result, the bacteria remain healthy and continue to cause infection and normal activity [15]. On the other hand, pathogenic bacteriophages replicate independently and destroy host cells. This contamination cycle is also called the bacteriophage lytic cycle. Therefore, these phages are used to kill bacteria and as therapeutic targets for infectious diseases (Fig. 1).

Fig (1). Important events related to phage and phage therapy research in recent years [19, 20].

In 1919, bacteriophages were used to treatment of bacterial infections in Eastern Europe and the former Soviet Union. Nevertheless, in the west, phage therapy was not taken seriously [17]. In addition, in the west, a lack of knowledge about the biology of bacteriophages was the main reason for not using phage therapy. In 1915, bacteriophages were first observed in the bacterial environment by a British researcher. Also, in 1920, Dehler was able to identify the mechanism of phage science and report on the biological function of phages. So, in the 1920s and 1930s, the focus on phages in bacteriophage therapy programs peaked in the United States. In addition, an American company called Lily was able to produce a gel called Staphylococcusgel, which is labeled with bacteriophages. Furthermore, Abbott Laboratory succeeded in producing filters equipped with phage particles. Over the next years, researchers were able to discover the antibiotic properties of phages against bacterial infections [18].

In addition, between 1950 and 1980, many articles were published on phage therapy. Also, this trend continues from 2014 to 2016. Furthermore, with the keyword Phage therapy, more than 15,000 information records in the ISI appendix are available to users. Therefore, the high volume of information indicates the practical importance of phages in limiting infectious agents [19]. MedPage is one of the most important antibacterial drugs produced by pharmaceutical companies using phages to fight bacterial infections. Therefore, MediPhage is currently approved by the Food and Drug Administration (FDA) as an effective drug in limiting bacterial infections. Summary of the important events related to phage and phage therapy research on the length of time in (Fig. 1).

Currently, five groups of phages are used as appropriate targets in research laboratories in the treatment of bacterial infections. In addition, phages with brand names, Bacte-pyo-phage, Bacte-intesti-phage, Bacte-rhino-phage are available as effective phages in phage therapy [21]. Hence, Bacte-staphy-phage and Bacte-coli-phage are used against bacteria such as Escherichia coli, Streptococcus, Staphylococcus and other bacterial agents that cause infections in humans. Furthermore, some phage-derived compounds are produced to reduce the rate of infection caused by infectious bacteria. So, these compounds include antholysate, niso-lysate, collo-lysate and staphyl-lysate. Also, phage-derived compounds are the most effective ones used in phage preparation [22].

Many reports point to the same antibacterial properties of phages and antibiotics [20, 22]. In addition, much evidence suggests the same of phages and antibiotics [21, 22]. However, various studies demonstrated that phages have favorable therapeutic effects more than antibiotics. Hence, phages for the preparation of medicinal compounds can be considered more effectively in the treatment of infectious diseases. In addition, phage compounds can able to limit the spread of infectious diseases in humans with lung infections by S. aureus [23, 24].

Hence, research was conducted in the clinical phase using human samples. Also, sampling was performed in two groups A and B, that were patients with infectious diseases and was a statistical population of 223 and 117, respectively. Also, antibiotic treatment and phage therapy were applied. The results were demonstrated; the use of bacteriophages more effectively could limit the spread of the infection disease among these people [24]. The results study showed that phage therapy accelerates the treatment of infectious diseases and the resistance of bacteria in this group is also reduced [23].

However, the main problem in treating infections caused by pathogenic bacteria is antibiotic resistance. So, the treatment of bacterial infections with specific phenotypic conditions is a major problem. Today, biofilm formation by large bacterial populations is one of the biggest challenges for the treatment community [25-28].

On the other hand, Bacterial biofilms are a complex community of bacteria enclosed in a glycocalyx coating that adheres to the mucosal surfaces. Also, the development of biofilms can cause bacterial resistance to antimicrobial agents. In addition, biofilms in hospitals cause contamination and transmission of infectious diseases. In addition, Bacterial biofilm causes 80% of microbial infections. So, antibiotic treatment and eradication of bacterial biofilm are extremely difficult. In addition, biofilm plays an important role in nosocomial infections and urinary tract infections that can cause chronic infections. Also, chronic infection due to biofilm formation can make a huge burden in health care systems [26, 29].

Bacteriophage, as a natural and non-toxic antimicrobial compound, has found a special place in various industries. One of the new uses of bacteriophages is against biofilm-producing bacteria. In recent years, studies were performed to replace chemicals with bacteriophages to remove biofilm-producing agents from surfaces [27]. According to the evidence, various studies on the use of bacteriophages in the removal and control of biofilms of pathogens such as Klebsiella pneumoniae, Listeria monocytogenes, Pseudomonas aeruginosa and S. aureus in culture medium have been successful [30]. Also, the effectiveness of bacteriophages on biofilm is considered to be influenced by bacteriophage characteristics such as biofilm formation environment and type of bacteria and bacterial characteristics [31] (Fig. 2).

Evidence demonstrated that by genetically manipulating the bacteriophage, the binding way the bacteriophage to the host can be changed. So, the host of the M13 filament phage is E.coli. Also, phage M13 is altered by special techniques to be able to bind to H. pylori. Also, various fragments of an antigen-binding chain were amplified in mice and produced monoclonal antibodies against H. pylori. On the other hand, these fragments were expressed as g₃p binding protein on the surface of phage M13. So, this recombinant phage was able to kill different strains of H. pylori. This technology will be used in places where a high virulence lytic phage cannot be found for a specific bacterium [31, 32].

Today, the challenge of bioterrorism is becoming one of the most controversial issues in the entire world [32]. In addition, bioterrorism is the use of biological weapons to carry out destructive acts against humanity including in various forms, including the use of transgenic animals, genetically engineered bacteria, contaminated food, and dangerous toxins. So, weapons of mass destruction, including nuclear weapons, biological agents, chemical agents, incendiary weapons or other unconventional weapons, have the potential to threaten health, safety, food and the environment. So, in biological warfare, microorganisms and their associated toxins are used to produce disease and death in humans. Also, bioterrorism is a terrorist activity in which biological agents are used to assassinate individuals [33].

Unlike conventional weapons, biological agents can destroy agricultural products, cause food poisoning and contamination of medicinal products. However, because phages effectively kill pathogenic bacteria, these microorganisms can be used to counter bioterrorism threats. Although there is still no tool in society to deal with the threat of bioterrorism, it seems that due to the high potential of phages to eliminate bacterial contamination, these microorganisms can soon help treat infectious diseases [32, 33].

Fig (2). Schematic figure of phage therapy against bacterial biofilm formation [25-27].