The Prospective Role of Bacteriophages in Human Health

Posted on 2024-11-05

In recognition of World Phage Week, which ran from the 22nd of October to the 28th of October, Abbexa highlights the role and importance of bacteriophages. First discovered in the early 20th century by Frederick Twort and Félix d’Hérelle, bacteriophages - referred to as phages - have more recently gained recognition as agents for combating pathogenic bacteria (1,2).

Bacteriophages are the most abundant viral entity on the planet, present in every ecosystem ranging from extremely hot to extremely cold environments (3,4). These have the unique capability of infecting and decimating bacteria, where a single phage particle can hunt for a specific bacterium species. Once the bacterial cell is infected, phages multiply exponentially using the host’s cellular machinery (5,6).

Propagation methods may be either lytic or lysogenic. In particular, lytic phages cause the lysis of the host bacterial cells, whereas lysogenic phages integrate their genome within the host bacterial cell and replicate along with the host, conferring new properties to the host bacteria (7,8).

Phages have an icosahedral shape with a typical feature of a ‘head’ or capsid and a ‘tail’ (9). The ‘head’ structure, regardless of shape or size, is a congregation of one or more proteins that protect the viral nucleic acid (genome). The ‘tail’ is a hollow tube by which the nucleic acid can pass once the phage infects attaches to a bacterial host cell. Some phages do not possess a tail, and others have additional structures (10).

Specific receptors on the surface of the host bacteria are required for infection. Further, phages can only infect specific hosts, due to the specificity of the receptors on the bacterial cell surface. However, there are numerous aspects that determine a successful phage-host cell attachment, making it somewhat random. For example, the bacterial type, its growth conditions, and its virulence can influence the attachment of the phage (11).

For Gram-negative bacteria, an external lipopolysaccharide layer and embedded outer membrane proteins act as phage receptors, and in some infection strategies, are essential for the absorption of phage particles. In comparison, in Gram-positive bacteria, teichoic acids present in the cell wall act as receptors for corresponding phages. The insertion of nucleic acid varies per bacteria and phage group. As an example, Myorividae phages use a syringe-like movement of its tail, that will allow for the attachment of phage particles to the bacterial surface. On the contrary, Podovirae phages, devoid of the ‘tail’, insert their genetic material after enzymatically degrading a portion of the bacterial cell membrane (12).

Virulent phages, corresponding to phages in a lytic phase, cause the lysis of the host bacterium as the phage multiplies in great numbers within the host cell, causing the disintegration and rupture of the host cell for the release of new phage particles. The lysogenic phase is exhibited in particular by temperate phages and results in the integration of the viral genetic genome with the bacterial genome. Consequently, ensuring continued replication of the viral genetic material without any fatal consequences to the infected host. However, the integration of viral genetic material causes changes in the phenotype of the bacteria and can induce bacterial pathogenicity causing new bacterial strains to form (13).

Due to their function and the elevated use of antibiotics, leading to rising antimicrobial resistance, phages have regained recognition as a substitute for antibiotics. In 2001, “phage therapy” became a potential therapeutic option. Recently, the application of “phage therapy” has been used for the treatment of open wounds and burn injuries. Enterobacteriaceae, which include E.coli, Salmonella, and other Escherichia species, have been shown to develop resistance to conventional antibiotics (14).

Abbexa supports these advancements by offering a range of bacteriophage products, including T1 Phage Resistant Chemically Competent Cells, and specific antibodies such as the Bacteriophage M13 Capsid Protein G8P and Enterobacteria Phage T7 RNA Polymerase. These tools support the research in phage therapy and antimicrobial resistance.

References:

1. Herelle F d’, Smith GH. The bacteriophage and its behavior. The bacteriophage and its behavior. 1926 Nov 18;

2. Twort FW. THE DISCOVERY OF THE ‘BACTERIOPHAGE.’ The Lancet. 1925 Apr 18;205(5303):845.

3. Säwström C, Lisle J, Anesio AM, Priscu JC, Laybourn-Parry J. Bacteriophage in polar inland waters. Extremophiles [Internet]. 2008 Mar 10 [cited 2024 Oct 28];12(2):167–75.

4. Lin L, Hong W, Ji X, Han J, Huang L, Wei Y. Isolation and characterization of an extremely long tail Thermus bacteriophage from Tengchong hot springs in China. J Basic Microbiol [Internet]. 2010 Oct 1 [cited 2024 Oct 28];50(5):452–6.

5. Jamalludeen N, She YM, Lingohr EJ, Griffiths M. Isolation and characterization of virulent bacteriophages against Escherichia coli serogroups O1, O2, and O78. Poult Sci. 2009 Aug 1;88(8):1694–702.

6. Young R, Wang IN, Roof WD. Phages will out: Strategies of host cell lysis. Trends Microbiol [Internet]. 2000 Mar 1 [cited 2024 Oct 28];8(3):120–8.

7. Inal JM. Phage therapy: a reappraisal of bacteriophages as antibiotics. Arch Immunol Ther Exp (Warsz) [Internet]. 2003 Jan 1 [cited 2024 Oct 28];51(4):237–44.

8. Karlsson F, Borrebaeck CAK, Nilsson N, Malmborg-Hager AC. The mechanism of bacterial infection by filamentous phages involves molecular interactions between TolA and phage protein 3 domains. J Bacteriol [Internet]. 2003 Apr [cited 2024 Oct 28];185(8):2628–34.

9. Bacteriophage [Internet]. [cited 2024 Oct 28].

10. Leiman PG, Kanamaru S, Mesyanzhinov V V., Arisaka F, Rossmann MG. Structure and morphogenesis of bacteriophage T4. Cellular and Molecular Life Sciences [Internet]. 2003 Nov [cited 2024 Oct 28];60(11):2356–70.