Describe the bacteriophage with its life cycles and importance in microbiology.

Definition and Structure

• Typical structure (T-even phages) — a head (icosahedral capsid containing the nucleic acid), a tail with a contractile sheath, a base plate, and tail fibres that recognise specific receptors on the bacterial surface
• Host specificity is very high — a given phage infects only particular species or even strains, which is the basis of phage typing
• Discovered independently by Twort and d'Herelle, who named them for their ability to "eat" bacteria

Lytic and Lysogenic Cycles

Adsorption — tail fibres attach to a specific receptor → penetration — the sheath contracts and nucleic acid is injected; the protein coat remains outside (the basis of the Hershey–Chase experiment showing DNA is the genetic material) → The pathway now divides → lytic cycle — phage DNA takes over host machinery; new phage components are synthesised and assembled; the cell lyses, releasing progeny. Such phages are virulent → lysogenic cycle — phage DNA integrates into the bacterial chromosome as a prophage and replicates with it silently. The phage is temperate and the bacterium is lysogenic → The prophage may later be induced by UV light or chemicals to enter the lytic cycle

Importance in Microbiology

• Lysogenic conversion — as above, and of the greatest medical importance
• Transduction — phages carry bacterial DNA from one cell to another, transferring resistance and virulence genes; generalised transduction packages any fragment by error, and specialised transduction moves genes adjacent to the prophage site
• Phage typing — strains within a species are distinguished by their pattern of susceptibility to a set of phages. Used epidemiologically for Staphylococcus aureus, Salmonella Typhi and Vibrio cholerae to trace outbreaks and identify a common source
• Molecular biology tools — phages are used as cloning vectors, in phage display, and the CRISPR system (now a genome-editing tool) originated as a bacterial defence against them
• Detection of specific bacteria — phage amplification assays for mycobacteria

Phage Therapy

• The use of lytic phages to treat bacterial infection, developed in Eastern Europe and largely abandoned in the West after antibiotics appeared, and now under renewed investigation because of antimicrobial resistance
• Advantages — highly specific, so the normal flora is spared; they replicate at the site of infection, so the dose is self-amplifying; they are effective against multidrug-resistant organisms and can penetrate biofilms; and new phages can be isolated relatively quickly
• Limitations — the very specificity that is an advantage means the organism must be identified and a matching phage found; bacteria develop resistance to phages as readily as to antibiotics; the immune system clears them; lysis releases endotoxin; and regulatory frameworks are not designed for a self-replicating, individualised treatment
• Current status — used compassionately in individual cases of resistant infection with some striking successes, with formal trials in progress; not yet established practice

Applied Aspects

• Phage typing traces outbreaks to their source, which is how staphylococcal and typhoid outbreaks have been linked to particular carriers and food handlers
• Toxigenicity must be tested, not assumed — a strain of C. Diphtheriae is confirmed as toxigenic by the Elek test or PCR for the tox gene, since a non-lysogenised strain is harmless
• Phage-encoded toxins explain why some E. Coli cause haemolytic-uraemic syndrome, and why antibiotics may worsen it by inducing the prophage and increasing Shiga toxin release
• Interest in phage therapy is driven by resistance, and India's high burden of multidrug-resistant infection makes it a plausible area of future practice
• Molecular typing has largely replaced phage typing in well-resourced laboratories, but phage typing remains cheap and useful where sequencing is unavailable
• The history is instructive — a promising treatment was abandoned because a better one appeared, and is being reconsidered because the better one is failing; therapeutic options are rarely obsolete for ever