TD:Bacteriophages

Question 1

What are bacteriophages

Example?

Answer 1

Bacteriophages are bacterial viruses i.e. obligate intracellular bacterial parasites e.g. E.coli T4 phage

Question 2

Advantages and limitations of bacteriophage treatment?

Answer 2

• Strain specificity of phage limits damage to the host’s normal microflora but requires the pathogen to be characterised to strain level prior to beginning treatment and for there to be a specific phage available.
• Phage can be easily and quickly isolated.
• Development of a phage is less costly than for an antibiotic.
• There are a very large number of potentially useful phage still to be characterised.
• However bacteria can rapidly develop resistance to phage by several mechanisms including alteration to binding receptors.
• Bacteria are naturally in a continuous arms race with bacteriophages.
• Phage cocktails help to slow down the development of resistance.
  
  • Phage cocktails may however have a greater impact on normal flora.
• Even without using phage cocktails resistance may be less of an issue than for antibiotics ……the sheer number and variety of phage potentially available (estimated 1031 phage “species” ) means we are unlikely to run out of new infectious phage to treat pathogens.
• Phage+ Antibiotic combinations have also been explored….. sub-lethal levels of cell division inhibitors in combination with phage can make treatment more effective by increasing the phage’s lytic power and ability to spread.
• It can be difficult to maintain a high enough phage level in the circulatory system since the immune system perceives them as invaders and attempts to remove them.
• In the West, a specific regulatory framework for phage therapy has yet to be put in place.
• There is also a difficulty obtaining intellectual property rights for phage products.
• Phage may be lytic or lysogenic. Lysogenic phage incorporate their nucleic acid into the chromosome of the host bacteria without destroying the bacterial cell.
• Lysogenic could therefore, potentially, carry e.g. antibiotic resistance genes between bacteria and transfer them to pathogens. This, of course, must be avoided.
• To help prevent this only obligatory lytic, non-transducing phage, propagated on cells lacking virulence genes, are used.
• These types of phage have not however been identified for some pathogenic bacteria e.g. Mycobacterium tuberculosis.
• Large amount of material released by cell lysis may cause an inflammatory response e.g. by the release of endotoxins with serious side-effects to the host e.g. septic shock.

Question 3

Why might bacteriophage genomic engineering be useful?

Answer 3

Genetic modification of phages could help overcome many of the limitations of this potential therapy, including problems with patenting and spark the interest of large pharmaceutical companies.

Public hostility to genetic engineering could however be a barrier.

Question 4

Examples of current phage application

Answer 4

In 2006 the US FDA licenced a phage product for antimicrobial application. The product is a cocktail of 6 specific phage for Listeria monocytogenes and is applied as a spray to raw meats as a preventative measure to protect against listeriosis.

There have been a number of trials including for chronic otitis caused by P. aeruginosa in a biofilm. The phage treatment achieved an 80% decrease in bacterial counts. Also trials are underway on wound treatments.