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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
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.
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.
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.
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.
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
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