Bacteriophage, An Alternative To Antibiotics

By:- Bijayalaxmi Nongmaithem / Ajit Kumar Ngangbam *

INTRODUCTION

Bacteriophages or the phages are the virus that infects bacteria. Phages like all viruses are composed of a nucleic acid core surrounded by a protein coat. The majority of phages contain DNA but some contain RNA also. Phages are more resistant to physical and chemical factors than human viruses. The research of the bacteriophage phenomena has some exceptional importance in the history of microbiology.

The simplicity of their cultivation, short generation and exact accountability help to clarify not only the structure but also the relationships between the bacteria and viral particles. Since bacteriophages are the smallest entities known which are capable of self-replication, they have been widely used in genetic research.

Much has been learned about host-parasite relationships from the studies of bacterium- bacteriophage interaction. This provides a better understanding of plant and animal infection with viral pathogens. Thus the bacterium-bacteriophage interaction has become the model system for the study of viral pathogenicity.

There is interdependency between the bacteriophage and the microbial cells. Bacterial virus occurs in different shapes. Most of the phages have tail through which they inoculate the host cell or bacteria with viral nucleic acid. Bacterial virus are categorized into lytic and lysogeny. Lytic phages can infect the cells and the cells respond by producing large number of new virus.

At the end of the incubation period, the host cell bursts and released new phages to infect other host cells. In lysogenic ones, the viral nucleic acid is carried and replicated along with the host bacterial cells from one generation to another without any cell lysis. These phages may become virulent at some subsequent generation and can lyse the host cells. There are also filamentous phages which simply leak out of the cells without causing any lysis.

The interaction usually ends with the destruction of the microbial cells. It is important to note that bacteriophage are host specific and have no adverse affects on humans, animals or to the environment.

Figure: Bacteriophage

DISCOVERY OF BACTERIOPHAGES

The history of bacteriophages discovery has been a lengthy debate. It starts with the reports on the presence of marked antibacterial activity against Vibrio cholerae in the water of the Ganges and Jamuna River in India as reported by Ernest Hankin (1896). This antibacterial substance can pass through fine porcelain filter and responsible for limiting the spread of cholera epidemics.

Two years later, the Russian bacteriologist, Gamaleya, observed the same phenomena while working with Bacillus subtilis. Almost twenty years later of Hankin's observation, a British bacteriologist, Frederick W. Twort in 1915, actually isolated filterable entities capable of lysing bacterial cultures and producing small cleared areas on bacterial lawns (Twort, 1915).

Two years later of Twort discovery, Felix d' Herelle, a French Canadian microbiologist at the Pasteur institute in Paris reported the same phenomena and Felix d' Herelle officially named it as bacteriophage (d' Herelle, 1917). The credit for discovery of bacteriophage remains disputed to this day. This priority dispute ceased eventually and many scientists accepted the independent discovery of bacteriophages and simply referred to it as the "Twort- d' Herelle phenomenon" and later the "bacteriophage phenomenon".

BACTERIOPHAGE IN FRESHWATER ENVIRONMENTS

Freshwater environments contain a variety of micro-organisms. They may interact in parasitic, symbiotic or commensal relationships. These environments also contain sub cellular entities, viruses. Bacterial virus is also found in these environments. In most of the studies of the distribution of phages in freshwater environment, strains of E. coli have been used as host bacteria.

This likely reflects the interest expressed in the possibility of using E. coli phages (coliphages) as the indicator of enteric virus of bacteria. Enteric bacteria other than the E. coli and indigenous coliform bacteria may also be present in freshwater environments. Therefore it would be expected that phage active against these bacteria would also be recovered from these water.

Although relatively few workers have studied these phages, phages active against Klebsiella pneumoniae and Salmonella spp. were also recovered from freshwater. They were found in numbers comparable to those of E. coli. There are several factors that have the potential to influence the number and activities of bacteriophage in freshwater environments.

These include the densities of both host bacteria and their phage, the association of bacteria and phage with solids, the presence of organic matter especially the organic matter that influences the metabolic activity of the host bacteria, ultraviolet light and visible light, temperature, ph, the concentration and types of ions and the metabolic activity of the micro-organisms other than the host bacteria.

BACTERIOPHAGE THERAPY

Bacteriophage therapy is the therapeutic use of bacteriophages to treat pathogenic bacterial infections. The potential benefit of phage therapy is that bacteriophages can be much more specific than more common drugs, so they can be chosen to be harmless not only to the host organism like human, animal, or plant, but also to other beneficial bacteria, such as gut flora and reduce the chances of opportunistic infections due to its high host specificity.

The emergence of pathogenic bacteria resistant to most, if not all currently available antimicrobial agents has become a critical problem in modern medicine, particularly because of the concomitant increase in immunosuppressed patients. The concern that mankind is re-entering the preantibiotics era has become very real and the development of alternative anti-infection modalities has become one of the highest priority of modern medicine and biotechnology. This leads to the concept of phage threatment.

Prior to the discovery and widespread use of antibiotics, it was suggested that bacterial infection could be prevented by the administration of bacteriophage. The bacteriophage co-exists in the same environment as where microbes are reproducing. The bacteriophage can be found everywhere in humans and animal intestines, in running water, in the soil or in the cell of microbes.

One of the most important properties of bacteriophage is its host specificity and its accompanying ability to distinguish types among apparently identical serotypes. In order to have a successful phage therapy, it is important to isolate species or strain specific phages. For treatment, the phage preparation should be tested for rapid clearance by the immune system of the animal body.

The development of phage resistance by target bacteria is also an important issue which needs to be carefully addressed while developing a phage therapy. Careful merging of the scientific methodologies along with present available knowledge and information can help to design a successful strategy as phage therapy.

BACTERIOPHAGE Vs ANTIBIOTICS

ADVANTAGES

Bacteriophages	Antibiotics
* Developing a new phage against phage-resistant bacteria is a fast process and can be accomplished in days. * Highly host specific affects the targeted bacterium only * No side effects have been reported so far * Easy to isolate phages and relatively inexpensive	Can be used without knowing exact characteristics of the disease-causing bacteria.

DISADVANTAGES

Bacteriophages

Antibiotics

It is necessary to identify the disease-causing bacterium before the application of phage therapy due to the high specificity of phages

* Antibiotics can affect the microbial balance in the gut, which, in turn, often leads to serious secondary infections due to non-specific action that targets not only the pathogenic microorganisms but also a normal micro flora of the healthy host * Development of Antibiotic resistant bacterial strain * Development of a new antibiotic against pathogenic bacteria is a lengthy process and may take several years * Production is expensive, may take several million dollars to develop an antibiotics

CONCLUSION

Bacterial viruses are widely distributed in nature. Phages exist for most, if not all, bacteria. With the use of proper techniques and method these phages can be isolated quite easily in the laboratory. Though the concept of using phages for controlling bacterial infection was coined in 1920s, several drawbacks associated with the technique have limited the use of this approach.

The emergence of antibiotic and multiple drug resistant bacteria is a major concern which emphasizes the need for alternate means of antibacterial therapy renewing the interest in phage mediated control of pathogenic bacteria. The phage treatment has extended from medical field to others such as agriculture, fisheries, food industry and waste water treatments.

The abundance of phages in the aquatic environment highlights their potential use for control of pathogenic bacteria in food and animals.

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* Bijayalaxmi Nongmaithem (College of Fisheries, Tripura) and Ajit Kumar Ngangbam (PhD scholar, Department of Microbiology, UNESCO Centre for Marine Biotechnology, College of Fisheries, Mangalore) regularly contributes to e-pao.net . Ajit Kumar Ngangbam can be contacted at ajit_b2007(at)yahoo(dot)co(dot)in
This article was webcasted at e-pao.net on 27th June 2009.

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