Bacteriophages are the third variables that are included other than man and Bacteria which are present in abundance in this biosphere. They are found to be of the prokaryotic origin. Bacteriophages are thought to play a very important role in causing bacterial infection by evolving many bacterial pathogens. The phages integrate their genome into the bacterial host genome and often results in the alteration in the properties in the bacterial cell, this is called as acquiring lysogeny and the process is called as phage conversion. Lysogenic cycle of Bacteriophages usually does not kill the host bacterial cells that they infect. The phage DNA is said to be the Prophage DNA and the phage is called Lysogenic phage and the host is called lysogenised host. A number of toxins present in Gram positive and the Gram negative organisms are encoded by these Bacteriophages. Some times Archae may be infected but this topic is quite debatable.
When the lysogeny is established the temperate phage integrates their genome into bacterial chromosome .The Lysogenic cycle contributes to the selective advantages to its bacterial host. The Phages are responsible to transfer some of the mobile elements or some other bacterial DNA. This review article would be dealing with the Contribution of the Lysogenic phages in the bacterial infection.
DISCOVERY OF PHAGE ENCODED GENES CONTRIBUTING TO THE VIRULENCE
The contribution of the Bacteriophages in the pathogenicity of its bacterial host remained undiscovered for a long time. Later the discovery of nontoxigenic Streptococci which when exposed to the supernatant that was filtered containing toxigenic Streptococcal culture, it was found that the nontoxigenic culture acquired the ability to become toxigenic and produced the scarlatinal toxin. The supernatant contained Bacteriophages which encodes for the scarlatinal toxin .This lead to the discovery of transduction (where in there is transfer of genetic material by means of phages). Over time it was found that these phages encode toxins and thus the production of toxin is one such role of phages in increasing the pathogenicity of the bacterial infection. However, Phages are also sometimes encoding genes which are required for transcription and replication which is followed by the phage induction. Some phages interms increase the expression of the virulence genes by encoding some of the regulatory factors. (Fujii et al, 1927)
The genes that the phage encodes are always not transmissible .This may be because of the fact that the integrated genome usually becomes more defective and also because of the technical limitations in detecting the transducing phages. Now-a-days the detection of the integrated genome by methods like sequencing it could be find out whether the integrated genome is of the phage origin or the bacterial origin regardless of whether they are transmissible or not. The non –transmissible gene stx of Shigella dysenteriae are present adjacent to the phage (lambda) like sequences that are interrupted by many insertion sequences .this proves that the toxin is present in a Prophage which have been rendered defective by the presence of the insertion sequences. However the transduction of the virulence gene is an insufficient evidence for proving that the gene is present in the phage genome. (Strockbine et al, 1988)
PHAGES AFFECT THE BACTERIAL COLONIZATION, INVASION AND ADHESION
The Bacterial infections involve various steps like adhesion, invasion and colonization. In different bacterial pathogens different phages are suppose to effect different steps in the bacterial infections. Streptococcus mitis which is responsible for endocarditis is a very good example of the phage mediated adhesion. The streptococci which are thought to be blood borne usually adhere to the platelets, matrix, platelets and thus giving rise to specific vegetation which can damage the heart valves and can become a source for bacteremia and sepsis. In this paper they decided to use the transposon mutagenesis to identify and prove the bacterial loci which is involved in the platelet adherence. They did identify a single locus which was encoding two different surface proteins which are PblA and PblB. They find out these gene sequences resembles mostly the phage tail fiber and capsid genes. Also these were surrounded by Phage like gene sequences. These genes are present in a phage which is inducible SM1. They encode the proteins of the SM1 particle. Disruption of either one of the PblA or PblB can cause a significant level of decrease in the binding of the organism to the platelets. However the mechanism of the phage particle that is associated in bacterial membrane bound fractions remains unknown and required further study (Bensing et al, 2001)
The bacterial invasions in the human tissues involve the help of certain bacterial enzymes which involve generally Hemolysins, collagenases and hyaluronidases. The hyaluronidase which is produced by the group A Streptococci is Phage encoded and the activity of this enzyme is associated with the phage particle itself. Hyaluronic acid comprise of the entire capsule of the group A Streptococci , This Hyaluronic acid capsule adds certain properties of the phage like penetration and release of the Streptococci during infection and thus the spread of the infection through the connective tissues. For the detection of the infection it is also possible to detect the antibodies to this hyaluronidase capsule in the serum of the patient who are infected with these streptococci (Hyder et al, 1978)
INCREASED RESISTANCE OF THE BACTERIA TO THE PHAGOCYTES IS PHAGE ENCODED.
Whenever there is a Bacterial infection, the bacterial pathogen generally enters in the serum where the phagocytic elements elevate the innate response. Staphylococcus is found to produce a large number of proteins that are involved in the phagocytic evasion. This also includes a inhibitor of chemotaxis CHIP .This protein binds increases the activity of the neutrophile for the production of formylated peptides and complement. This function is thought to be protective for streptococci and very important in inhibiting the host defense against it. The genes that encode these CHIPS are found to be present in a phage which transduce an enterotoxin & Staphylokinase and also eliminate the production of the beta-Hemolysins, mainly by the process of insertional inactivation. These Staphylococci is also found to produce a leukocidin which is encoded by the phage. This toxin directly inhibits the phagocytic activity. (Van der Vijer et al, 1972)
BACTERIAL EXOTOXINS ARE SOMETIMES PHAGE ENCODED
There are large numbers of examples for the virulence factors that have been experimentally proved to be phage encoded. One such good example is the Exotoxin. One major step i.e. involved in the elevation of pathogenesis of many bacteria involves production of Exotoxin. E.g.: The Cholera toxin which is produced by V.cholerae, C.botulinum, C.diphtheriae etc (Bishai et al, 1988)
PHAGES CAN ALSO PROVIDE INCREASE OR DECREASE SUSEPTIBILITY TO THE ANTIBIOTICS
We know that most of the resistance to a particular antibiotic that is acquired by a bacterium is encoded by the transposon and also by the plasmids. Till now no Phage encoded genes that provide resistance to a particular antibiotic were discovered. However, extensive research showed that these phages can be responsible for the mobility of these plasmids and transposon that encode the resistance to a particular antibiotic among the group of Streptococci and Staphylococci. The Phages have been found to transfer the non phage encoding resistance genes by generalized transduction and provide resistance against the various ranges of antibiotics lincomycin, chloramphenicol, tetracycline as well as streptomycin to some extent etc (Ubukata et al, 1975)
THE TRANSMISSION OF THE BACTERIAL PATHOGEN IS ENHANCED DUE TO THE PHAGE ENCODED PRODUCTS
The Cholera caused by V.cholerae produces a very powerful toxin that is found to up regulate the activity of the adenylate cyclase. This unregulated activity leads to watery diarrhea. Now this watery diarrhea is considered to significantly contribute to the fecal-Oral transmission of the pathogen .However this Cholera toxin is Phage encoded and thus this system is a very good example of a Bacteriophages that are contributing in transmission of the bacterial host among the humans. (Waldor et al, 1996)
CONTRIBUTION OF THE PROPHAGE INDUCTION IN VIRULENCE
Even though The induction of the prophage is thought to be responsible for the production for several virulence factors have been proved by in vitro experiments till not . However, there is a very little knowledge about the effect of the Prophage induction and production of the virulence factors during the coarse of infection. It is still convincible that various bacteria exist in a comparatively less virulent state unless they encounter a Prophage induction in a human body, only after which the virulence factors are produced and eventually which could contribute to the pathogenesis of the bacterium. This paper basically proves that insitu Prophage induction could perfectly explain when and where certain virulence factors are produced during the coarse of the bacterial infection. Moreover, the virions that are produced and released within the human body could definitely contribute to production of virulence factors and contributing to the pathogenesis. (Acheson et al, 1998)
BENEFITS TO THE PHAGE PROVIDED BY PRODUCTION OF THE VIRULENCE FACTORS
The production of the virulence factors by the bacterial pathogens may have effect the phage as well in a beneficial way. The hyaluronidase which is encoded and incorporated in the phages of S.aureus may facilitate and in terms increase the penetration of the capsule during the phage infection. Similarly is the case with O antigen alteration in the Gram negative organisms by the phages, This may also lead to the bacterial evasion , Provides advantages to the phages for causing superinfections on the resistant bacterial host. In some cases , the virulence factors are thpught to be the actual integral part of a phage particle. The CTXφ-encoded Ace protein, is seen in V. cholerae enterotoxicity which is a minor coat protein of CTXφ virion. Thus, these virulence Factorsare found to be the phage attributes the bacterial pathogenesis.
Conclusion
From the above review article we could explain that the Bacteriophages are extremely important and are involved in the bacterial pathogenesis. The phages provide the bacterium with the properties like adhesion, invasion, Exotoxin production etc. These Bacteriophages are largely contributing to the pathogenesis of the Bacterial pathogen by transduction of virulence genes. For the expression of these virulent gene, there is a requirement for the induction of the Prophage that encodes them. Because Prophage induction is required for the production of the virulence genes this makes the Lysogenic Phages ore important in Bacterial Pathogenesis.