Author:Author:Bhavana. BBhavana. BIII BDSIII BDS

Guide:Guide:Mr. G. HariprasadMr. G. HariprasadLecturerLecturer

Professor Professor & HOD:& HOD:Dr. R. RaghuramanDr. R. RaghuramanDepartment of MicrobiologyDepartment of MicrobiologyMeenakshi Ammal Dental CollegeMeenakshi Ammal Dental College

BACTERIOPHAGE THERAPY

“A Once and Future Solution”

DISCOVERY…

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.

1915 – Frederick Twort &

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

1920 – Isolated bacteriophages as antibacterial agents.

1930’s – Phage therapy was licensed for use.

Frederick Twort

Felix d’Herelle

EARLY 1940’s…..Bacteriophage 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.

“ONCE AND FUTURE SOLUTION!!!”

BACTERIOPHAGES ???

Simply called “Phages”.Felix d’Herelle – proposed the name

“Bacteriophage” . Derived from two words…. Bacteria Phagein – ( to eat or devour in Greek ) Implies that phages ‘eat’ or ‘devour’

bacteria.Bacterial viruses that invade bacterial cells and cause bacterium to lyse.Ubiquitous, obligate parasites.Natural, self limiting antibiotics.

STRUCTURE OF BACTERIOPHAGE…

Properties of phages…

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.

Different morphological forms…

Various shapes…

Filamentous phages…..

Two main groups of phages…….

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 phase of bacteriophages….

Lysogenic phase of Bacteriophages…..

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.

Mechanism…..Once administered….

Suitable host bacterium

It’s tail fibres bind to receptors on to the bacteria………..

Injects its strand of genetic material into the bacterial cell.

Bacteriophages

Meet

Two approaches to bacteriophage therapy…..

Intact phage therapy Therapies based on phage components.

i.e., Lysin therapy

Intact phage therapy

Whole phage products are 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 components

Phage 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.

Applications of phage lysin therapy

Bacillary Dysentery. Infections of skin and nasal mucosa Lung and Pleural infections. Inflammatory urologic disease Peritonitis, osteomyelitis and post-surgical wound infections. Rhinitis, Pharyngitis

On therapy… After 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

Phage therapy Vs Conventional antibiotic treatment…

High specificity.Normal gut microflora are not affected.Phage therapy is used as an alternative for people are allergic to antibiotics.Administered in different ways – pills, injections, enemas, nasal sprays, ointments.Single dose is often sufficient.Safe and efficient.Production is simple and inexpensive.Can be used either independently or in conjunction with antibiotics.

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.

Why can’t Phage

therapy be applied on

me???

Still a long way to go…..

AcknowledgementAcknowledgement

Dr. P. Jayakumar, Principal ( MADC)Dr. P. Jayakumar, Principal ( MADC)Dr. Ambalavanan, Vice Principal (MADC)Dr. Ambalavanan, Vice Principal (MADC)Dr. Raghuraman, Head, Dept of MicrobiologyDr. Raghuraman, Head, Dept of MicrobiologyA. S. Smiline GirijaA. S. Smiline GirijaG. S. ChamundeeswariG. S. ChamundeeswariVijyashree PriyadharshiniVijyashree PriyadharshiniG. HariprasadG. Hariprasad

Thank you………