This document discusses the history and current state of bacteriophage therapy. It begins by outlining the discovery of bacteriophages in the late 19th/early 20th century. It then describes how bacteriophage therapy was used commercially in the 1940s but declined with the rise of antibiotics. Recent antibiotic resistance has revived interest in bacteriophage therapy as an alternative approach. The document outlines the structure and life cycle of bacteriophages, and describes two main approaches to bacteriophage therapy - using intact phages or purified phage components like lysins. It discusses some potential applications and challenges to therapeutic use of bacteriophages.

2. Author:Author:
Bhavana. BBhavana. B
III BDSIII BDS
Guide:Guide:
Mr. G. HariprasadMr. G. Hariprasad
LecturerLecturer
ProfessorProfessor & HOD:& HOD:
Dr. R. RaghuramanDr. R. Raghuraman
Department of MicrobiologyDepartment of Microbiology
Meenakshi Ammal Dental CollegeMeenakshi Ammal Dental College

3. BACTERIOPHAGE THERAPY
“A Once and Future Solution”

4. 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.

5.  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

6. 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!!!”

7. 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.

8. STRUCTURE OF BACTERIOPHAGE…

9. 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.

10. Different morphological forms…

11. Various shapes…
Filamentous
phages…..

12. 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.

13. Lytic phase of bacteriophages….

14. Lysogenic phase of Bacteriophages…..

15. 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.

16. Mechanism…..
Once administered….
Suitable host bacterium
It’s tail fibres bind to receptors
on to the
Injects its strand of genetic
material into the bacterial cell.
Bacteriophages
Meet

17. Two approaches to
bacteriophage therapy…..
Intact phage therapy
Therapies based on phage
components.
i.e., Lysin therapy

18. 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.

19. 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.

20. “ 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.”

21. 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.

22. 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

23. 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

24. 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.

25. 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.

26. Why can’t
Phage therapy
be applied on
me???

27. Still a long way to go…..

28. 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 Microbiology
 A. S. Smiline GirijaA. S. Smiline Girija
 G. S. ChamundeeswariG. S. Chamundeeswari
 Vijyashree PriyadharshiniVijyashree Priyadharshini
 G. HariprasadG. Hariprasad

29. Thank you………