Bacteriophage

Viruses and Bacteriophage for higher education

Topic related resources

The word phage stems from the Latin phrase, 'to devour'. Bacteriophage then, are viruses that specifically infect and kill bacterial cells. The molecular biology of bacteriophage, and their specificity to bacterial cells make them amenable for use in a variety of research and therapeutic enviorments.

Introduction to viruses and viral taxonomy

Viruses are small, obligate, intracellular parasites. They are obligate because of their inability to replicate independently. Instead, they require the molecular machinery of a host, be it human, bacteria, archaea or plant. Typical viruses consist of a protein coat surrounding the viral genome. Viral genomes are extremely diverse and can consist of both double and single stranded DNA or RNA, they can be linear or circular and the RNA genomes can be either positive sense (directly translated into protein, similar to mRNA) or negative sense.

Viral taxonomy has long been a hotly debated topic, as they struggle to fit  the taxonomical systems we already have in place. One common method of viral classification is the Baltimore scheme (shown below), which groups viruses based on the structure and composition of their genomes. This scheme is particularly useful, as often the viral genome will reflect upon its method for genome replication, gene expression and life cycle.

The Baltimore Scheme

The balitmore scheme for viral classification. Viruses within the Baltimore scheme are grouped based on the composition of their genomes, and their method for genome replication.

Bacteriophage are viruses that specifically infect bacterial cells. Bacteriophage, even within similar Baltimore taxa are extremely varied, with wide diversity in both their genomic and coat structures.

Phage structure

Bacteriophage structures are diverse, but the vast majority of characterised phage share some common characteristics. Many phage have an icosahedral, head structure made of repeat protein subunits known as the capsid. This head structure contains the viral genome. The primary difference in phage are the presence or absence of a 'tail' structure.

Phage structure

Above - a diagrammatic representation of the structure of phage λ (lambda) which was the first and phage discovered, and perhaps the best characterised in the modern day.

The life cycles of phage

Phage, much like other eukaryotic viruses have two distinct life cycles. These are the lytic cycle, a productive process leading to synthesis of new phage particles, and the lysogenic cycle, a 'silent' stage where the phage genome is integrated with the host chromosome.

To begin their life cycle, phage must first come into contact with a bacterial cell encoding a receptor, complimentary to the phage anti-receptor. Once cell contact has been established, phage enter the bacterial cell and begin to either replicate, or establish state of 'silence'.

Note - phage from different Baltimore groups have different mechanisms of cellular entry, genome replication and exit from the cell. Here we are presenting a generic overview of the phage life cycle. Additional information on the topic can be found on the 'topic related resources' page.

Phage lack the machinery required to express their own genes and replicate their own genomes. They must therefore hijack this capability from the host cell machinery. Expression of phage genes, and synthesis of new phage particles form the lytic cycle.

The lytic cycle

In the lytic cycle, the host cell machinery express phage genes, forming coat proteins and replicate the phage genome. Coat proteins are then assembled around replicated phage genomes to form complete phage particles. As more and more phage particles are synthesised, the host cell eventually reaches breaking point and ruptures (lysis). Phage particles are then released into the surrounding area, ready to infect a new host. Once in the cell however, phage genomes can also integrate with the host chromosome, forming a state of lysogeny.

The lysogenic cycle

In the lysogenic cycle, the phage genome integrates with the host chromosome. Integrate phage genomes are known as prophage. Once in a state of lysogeny, phage can remain within their hosts for many generations. In order to transition from the lysogenic cycle, back in to the lytic cycle, gene expression must be stimulated. The best studies model of gene expression and lysogenic-lytic transition is that of bacteriophage lambda, reviewed in the article by Oppenheim et al.

The life of cycles of phage

Above - a diagrammatic representation of both the lytic and lysogenic life cycles of phage λ (Campbell, A. 2003).

Uses

Traditionally, phage have been studied as model organisms to gain insights into basic genetic concepts, such as viral gene expression (much of our understanding is derived from studies of phage λ). This is due to their ease of manipulation and culture. Now however, the focus is shifting to understanding the biology of phage themselves, and how they can be used in biotechnology and the treatment of infectious, bacterial disease.

phage therapy

As phage specifically infect bacteria, and not eukaryotic cells, their use as therapeutics against infectious disease is a key area of research. Several countries (including Russia and Georgia) already use phage to treat bacterial infections with varying success. As antibiotics have traditionally been more effective at treating bacteria infections, phage therapy has not been widespread. It's potential use is however under reinvestigation due mainly to the evolution of antibiotic resistant bacteria.

Note: bacteria can become resistant to phage infection. If you want to find out more, take a look at our tutorial investigating the role of phase variation in phage resistance of Campylobacter jejuni by clicking this link.

Biotechnology/research

The ability of phage to facilitate horizontal gene transfer by transduction has rendered them a valuable tool in biotechnology. Phage can be used to construct mutants in different species of bacteria by acting as vectors for foreign DNA. Many protocols now exist to use phage in molecular microbiology laboratories.

 

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