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The prospect for bacteriophage therapy in Western medicine

Nature Reviews Drug Discovery volume 2, pages 489–497 (2003)Cite this article

Abstract

Bacteriophage (phage) have been used for clinical applications since their initial discovery at the beginning of the twentieth century. However, they have never been subjected to the scrutiny — in terms of the determination of efficacy and pharmacokinetics of therapeutic agents — that is required in countries that enforce certification for marketed pharmaceuticals. There are a number of historical reasons for this deficiency, including the overshadowing discovery of the antibiotics. Nevertheless, present efforts to develop phage into reliable antibacterial agents have been substantially enhanced by knowledge gained concerning the genetics and physiology of phage in molecular detail during the past 50 years. Such efforts will be of importance given the emergence of antibiotic-resistant bacteria.

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Figure 1: Electron micrograph of phage.
Figure 2: Systemic distribution of phage following intravenous and oral administration of phage.
Figure 3: The effect of therapeutic phage concentration on morbidity and mortality.
Figure 4: Phage plaques on a bacterial 'lawn'.

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Authors and Affiliations

  1. Section on Biochemical Genetics, National Institute of Mental Health, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Carl R. Merril & Dean Scholl

  2. Section of Developmental Genetics, National Cancer Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Sankar L. Adhya

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DATABASES

Online Mendelian Inheritance in Man

Severe combined immunodeficiency

FURTHER INFORMATION

Encyclopedia of Life Sciences

Bacteriophages

bacteriophages in industry

phage display technologies

Genomes of the T4-like Phages

Phage Ecology and Evolutionary Biology

Phage Page

Phage Therapy

Therapeutic uses of phage

Glossary

ADAPTIVE IMMUNE SYSTEM

The arm of the immune system that mounts an antigen-specific immune response as the result of the clonal selection of antigen-specific lymphocytes. Such lymphocytes produce antibodies that react with the antigen. The adaptive immune responses differ from the innate and non-adaptive immune system, which does not depend on clonal selection of antigen-specific lymphocytes.

BIOFILM

A structure made up of a community of bacteria composed of microcolonies and water channels that survives at a liquid interface. Such biofilms play a role in the pathogenic effects of bacterial infections associated with gingivitis, colitis, vaginitis, urethritis, conjunctivitis and otitis.

ENDOTOXINS

Components of bacterial cells that are usually associated with the lipopolysaccharide components of the outer layer of Gram-negative bacterial cell walls that are toxic (to mammals). Endotoxins are released in large quantities upon lysis of Gram-negative bacterial cells.

ENDOSIALIDASES

Enzymes that cleave at the sialic acid residue sites of the complex oligosaccharides associated with the protective capsule of many bacterial strains.

EXOTOXINS

A broad class of factors released by pathogenic bacteria that can harm infected mammals. Examples of such exotoxins are botulism toxin (Clostridium botulinum), streptolysins (Streptococcus pyogenes) and diphtheria toxin (Corynebacterium diptheriae).

IATROGENIC

An effect that is induced in a patient by a physician's activity or therapy; such effects often occur as complications of treatments for infectious diseases.

LD50

The amount of a substance that causes the death of 50% of test subjects.

LYSATE

The colloidal bacterial growth media remaining after phage replicate and kill the host cells. Lysates contain phage progeny, bacterial cell wall debris and, often, internal cellular components (for example, proteins, nucleic acids, small molecules and so on).

LYSOGENIC PHAGE

Phage that are capable of integrating their genome (that is, lysogenize) into the host chromosome. Such phages often mediate horizontal gene transfer (transduction) between bacterial strains. Most lysogenic phage can also go through a lytic cycle to produce more phage, often after induction (from some environmental factor).

LYTIC PHAGE

Phage that infect bacterial cells to replicate and then lyse the bacterial host.

NEO-ANTIGEN

An antigen for which animals or humans being studied have no pre-existing antibodies. The phage φX174, which is highly immunogenic, has served as such a neo-antigen in studies of human antibody responses, as most humans have no pre-existing antibodies to this phage.

PHAGE

Bacterial viruses. The term phage is used as both singular and plural when referring to phage(s) that is/are member(s) of a single phage strain. However, when referring to phage in more than one strain the plural is phages.

PHAGE PLAQUE

The lesion formed when a phage particle is applied to a film of a susceptible bacterial strain that is growing on an agar surface. The lesion results from the infection of a bacterial cell by a phage particle, followed by the production of phage progeny and their release by lysis, followed by the infection and lysis of additional bacterial cells in the vicinity of the initial infection.

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Merril, C., Scholl, D. & Adhya, S. The prospect for bacteriophage therapy in Western medicine. Nat Rev Drug Discov 2, 489–497 (2003). https://doi.org/10.1038/nrd1111

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