Gland Institute of Pharmaceutical

SciencesFinal Seminar

By

Sai Kumar .V

Bacteriophage Therapy

An Alternative Path To Combat MultiDrug Resistance Bacteria

What are Bacteriophages? A bacteriophage is a virus that infects and

replicates within a bacterium.  Bacteriophages are composed

of protein that encapsulate a DNA or RNA. 1915 – Frederick Twort & 1917 – Felix d’Herelle – Recognised that some

viruses infect bacteria.

Different Shapes and types?

Plaque Morphology

Properties of Bacteriophages ? Highly specific – Each phage will attack only

one species or even a single strain of bacterium.

Shows different types of morphologies. Each phage has its own specific shape and

size. They are directly related to the number of

bacteria present. 12 distinct groups of phages, which are

diverse structurally and genetically. Common in all natural environments

‘’All these Properties make bacteriophage ideal for Treating the Drug resistant bacterial diseases’’

History of Phage therapy: 1896 – Ernst Hankin – Reported the presence of marked anti-bacterial activity against Vibrio cholerae in the waters of Ganga and Yamuna rivers in India and suggested that this was responsible for limiting the spread of cholera epidemics.

1917 – Felix d’Herelle – Recognised that some viruses infect bacteria.

1920 – Isolated bacteriophages as antibacterial agents.

1930’s – Phage therapy was licensed for use

Early 1940’sBacteriophage therapy was commercially used in the early 1940’s (Eli Lilly

Company – produced 7 phage products).

After the advent of antibiotics bacteriophage therapy came to a halt in most of the world.

Widespread development of antibacterial resistance provoked the need for new antibiotics and alternative strategies.

This resulted in rediscovery of bacteriophage therapy as a potent weapon against antibiotic resistant bacteria.

There are Two Main Groups of bacteriophages

Lytic phages• Instructs the machinery in

the host cell to make more bacteriophages

Lysogenic Phages• Phages attach their strands

of genetic instructions to the DNA of the bacteria. The phage DNA gets replicated along with the bacteria generation by generation.

Lytic Phage life cycle

Lysogenic phase life cycle

Bacteriophage Therapy???• Involves the use of phages or their products as bioagents for the

treatment or prophylaxis of bacterial infectious diseases.• Administration of phages: - orally through colon infusion - as aerosols - as injections: intradermal, intravascular, intramuscular,intraduodenal, intraperitoneal and even into lung, carotid artery and pericardium.

MechanismBacteriophages

Suitable host bacterium

It’s tail fibres bind to receptors on to

the bacteria

Injects its strand of genetic material into the bacterial cell.

There are two approaches to bacteriophage therapy:

Intact Phage Therapy Therapies Based on phage components

Eg:- Lysin Therapy

Intact Phage TherapyWhole phage is used

Used treat the infections of patients with antibiotic resistant bacteria.

Advantage : ‘amplification factor’ One phage enters a bacterium and replicates, releasing 10 to 100

phage particles after lysis, which then go on to enter and replicate in other bacteria and so on.

Problem: Development of resistance to phage attachment.Solution: Cocktail of phages designed to circumvent resistance. Other approaches to whole phage therapy are:

Use of phage deficient in their lytic system – can infect, replicate within and kill a target bacterium.

Use of whole phage as transport vehicles for delivery of lethal genes or chemically linked antibiotics, to target bacteria.

“ Although whole phage continue to generate interest as an alternative to antibiotics, focus is shifting to the use of purified phage components as antibacterial agents. ”

Therapies Based on Phage componentsPhage components that target the bacterium may provide boon to

anti-infective research.One of the most promising phage components currently under

development is a class of cell wall hydrolases termed LYSINS.Lysins are purified phage-encoded peptidoglycan hydrolases that

exhibit immediate and strong bacteriolytic activity when applied exogenously

Mechanism Of Lysin TherapyAfter specific trigger event in viral infection cycle

Lysins translocate into bacterial cell wall

Binds the major structural polymer – peptidoglycan

Cleavage of bonds required for stability

Hypotonic lysis

PROGENY RELEASE

Applications of Phage Lysin TherapyBacillary Dysentery.

Infections of skin and nasal mucosa

Lung and Pleural infections.

Inflammatory urologic disease

Peritonitis, osteomyelitis and post-surgical wound infections.

Rhinitis, Pharyngitis

PROBLEMS ASSOCIATED……….

Physicians need to make a specific diagnosis before prescribing a phage treatment.

Gastric acidity should be neutralised prior to oral phage administration.

There is a chance of spread of antibiotic resistance in bacteria.

THANK YOU