Bacteriophages - Viruses as Antimicrobials

VIRUSES AS ANTIMICROBIALS

BACTERIOPHAGES

Bacteriophages (phages) are viruses that infect only bacteria. They were first described at the end of the 19th century. They are typically 20–200 nm in size and are highly diverse in their structure and host range and it is likely that all bacterial species can be infected by a phage. Phages are extremely specific in their host range and some will only infect a specific bacterial strain. Such a high specificity is used for bacterial typing as discussed below. The most studied phages are complex ones (e.g. T-phage) sometimes referred to as ‘tadpole-shaped’ consisting of a head (often icosahedral) that contains the viral genome and a tail which function is to recognize the host receptor, attach and subsequently serve as a nucleic acid injection device (Figure 5.5). Indeed, one of the main differences between such phages and common mammalian viruses is that these phages inject their viral genome inside the host cell.

Phages have proved to be very useful genetic tools over the years, since they are easy to propagate to high concentration and easy to study. Because of their similarity to mammalian viruses, it is not surprising that phages have been used to elucidate the viral multiplication cycle and their study has led to many discoveries such as mRNA, the understanding of the genetic code and the control of genes, contributing to important advances in molecular biology.

From the study of phage replication cycles, two scenarios have emerged, one resulting in the lysis of the bacterial host—the lytic cycle—and the other resulting in the viral nucleic acid being integrated into the host genome—the lysogenic cycle (Figure 5.6). Infection with a lytic phage, also called virulent phage, results in the replication of the phage within the susceptible bacteria and the release of infectious phage progeny from the host cell following cell lysis. Such a lytic property is used to enumerate phages. Phages inoculated on to a lawn of a susceptible host bacterium form clear ‘holes’ (plaques) which result from phage infection and lysis of a bacterial host and the release of phage progeny, subsequently infecting, replicating in, and lysing adjacent cells, ultimately forming these plaques which are easily identifiable with the naked eye (Figure 5.7 ). Since each of these plaques is assumed to result from the infection from a single phage, the number of plaques counted is used to represent the number of phages.

In the lysogenic cycle, the viral nucleic acid which has integrated the host genome is called prophage, and the host cell that contains the viral genome lysogenic. Following infection with lysogenic phages, both a lytic and lysogenic responses are observed. The integration of the prophage ensures that the viral genome is passed on to the daughter cells following bacterial cell replication. Lysogeny is an extremely common phenomenon and through evolution most bacteria will host several prophages. Indeed, sequencing of the whole bacterial genome often indicates the presence of prophages (or their remnants), that have become disabled with time. On occasions, a prophage dormant in its host can be reactivated and resume a lytic cycle. Upon excision from the host genome, the prophage can take adjacent bacterial genes that become incorporated in the virion and transmitted to a new susceptible host cell. Genes carried on the prophage can then be expressed in the new host. This process is called transduction and is responsible for gene transfer between bacteria. Sometimes, genetic factors transferred by transduction encode for antibiotic resistant determinants and/or virulence factors such as toxins. The induction of prophages to a lytic cycle can be artificially triggered by exposure to chemical and physical agents such as mitomycin C and ultraviolet light. If the use of lytic phages might be appropriate to kill bacteria, the use of lysogenic phages is best confined to the genetic engineering of bacteria.