Merhan Mohammed GalalMicrobiology specialist at DRC

Antibiotic resistance Bacteriophage Phage therapy Bacteriophages vs Antibiotics Limitation and challenges

The ability of bacteria and other microorgan-isms to resist the effects of an antibiotic to which they were once sensitive.

What causes antibiotic resistance?

using antibiotics when they are not needed

not taking antibiotics at the doses and times that a doctor prescribes — this allows time for the bacteria in your system to be-come resistant

viruses that only infect bacteria and attack only a single bacterial strains. This specificity together with the killing capacity makes them the natural enemies of bacteria.

Phage head: composed of coat protein and genome in the core.

Tail sheath: DNA travels from head to bacterial sheath.

Tail fiber: helps anchor the phage on the cell membrane.

Lytic: phage lyse host bacterium

Lysogenic: integration of phage genetic material

French Canadian microbiologist Felix d’Herelle, first observed in 1910 the bacteriophage phenomenon

In 1917 he began testing his phages in human pa-tients administration them to a 12 year old boy with severe dysentery resulting in complete recovery.

Eli Lilly began to commercialize phage therapy in the US in the 1940’s.  However, when antibiotics were produced in the 1950’s they were widely marketed and became the cornerstone of the pharmaceutical companies business.  This put an end to research and development of phage therapy in the US and much of Europe.

The Soviet Union continued to use phage therapy and conducted many successful trials but there publications were mainly in Russian or Georgian languages and were unavailable internationally until recent years.   The thorough research done over the last 80 years does indicate an 80-95% success rate with very minimal side effects.

Phage therapy:

Using phages or their products as bioagents for the treatment or prophylaxis of bacterial

infectious disease.

Phage therapy has many potential applica-tions in human medicine as well as dentistry,vetrinary science and agriculture.

In human and animal intestine. In running water In the soil Effluent outlets Sewage from corpses

Very specific Target normal flora and pathogens

Abundant in environment Synthetic or semisynthetic

no side effects have been reported

Have sever side effects like allergies and secondary infection

Replicate at the site of infection

Travel throughout the body and don’t concentrate at the site of infection

Cheap to produce Antibiotic development may take several years, may cost millions of dollars

Good alternative for patients allergic to antibodies

If patient is allergic to antibiotic, treatment is very difficult

Their action is bactericidal Some are bacteriostatic

Immunogenicity: in prolonged treatments has been observed a development of antibodies against phages.

Contamination of therapeutic phage prepara-tions with endotoxin from bacterial debris.

Because of the high specificity of phages, the disease causing bacterium has to be identified before the administration of phage therapy.

Restriction: bacteria protect themselves by chopping up any foreign DNA by nuclease enzyme that strict the infection of phages.

Rapid clearance of phage by spleen.

This therapy cannot be used for intracellular bacteria as the host is not available for interac-tion

Proper storage of phages can be difficult. Freez-ing, high temperature or long storage with cool-ing may result in phage degradation.

the public’s negative view of viruses.  There will take some education to cross the “psychological barrier” that people have so they will not be worried about using these live viruses as a healthful tool.   We can look to Phages as the equivalent of probiotics and perhaps even title them as “proviriotics.”

Phage cocktails. Drug delivery technologies can enhance systemic

phage delivery and reduce phage inactivation and clearance.

Bacteria can be engineered to target intracellular defense pathogens.

Phages prepared from bacteria would need to be purified to diminish contamination of phage preparations with endotoxin and exotoxin .

Possible solutions

Living phages

Non replicating genetically modified phages

Phage lysin

Protein antibiotics

Types of bacteriophage therapies

The Food and Drug Administration approved the use of bacteriophage for use in food safety in 2006. Specifically to remove Listeria monocytogenes bacteria from cheese production. The following year the use of bacteriophage was approved for use on ALL food products.

Success in phage therapy

PhagoBioDerm, Markoishvili et al., 2002

Leg ulcer before phage therapyAfter therapy

Media Interest –24thJuly 2010Special