Overview on the History of Phage Therapy until today

1. PRESENTED BY,
ARNAB GUPTA KABIRAJ
M.Sc. MICROBIOLOGY SEMESTER – III
ROLL NO – BURMICRO 2016/002
REGISTRATION NO. – 001765 OF 2013-14
THE UNIVERSITY OF BURDWAN
HISTORY OF
THE
FORGOTTEN
CURE
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2. PHAGE
Definition - Bacterial viruses that invade bacterial
cells, infect bacteria by injecting genetic material
& causes lysis.
Highly specific, has its own specific shape and size,
consists of ssDNA/dsDNA or ssRNA/dsRNA molecule
encapsulated inside a protein coat, ubiquitous, obligate
parasites, causes lysis or lysogeny of bacterial cell.
The term “Bacteriophage” is derived from two word….
Bacteria & the Greek word - Phagein which means to eat
or devour.
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3. PHAGE THERAPY
Phage therapy - The therapeutic use of bacteriophages to treat
pathogenic bacterial infections.
Involves the use of phages or their products for the treatment of bacterial
infectious diseases.
Can be administered orally and topically on infected wounds
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4. HISTORY
a. 1896 – Ernest Hankin ,a English bacteriologist, reported presence of antibacterial activity
(against Vibrio cholerae ) in waters of Ganges and Jamuna rivers in India and he
suggested that an unidentified substance was responsible for this phenomenon and for
limiting the spread of cholera epidemics.
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Ernest Hankin

5. CONTD……
b. 1915 – Frederick Twort discovered entities capable
of destroying bacterial culture and of
producing small clear zone on bacterial lawns
but did not pursue his discovery.
c. 1917 – Félix d'Herelle independently
discovered the similar entities, he named
these as bacteriophage, investigated it the
and explored their ability to function as
therapeutic agents.
d. 1921 – First administration of phages was
given at the Hospital in Paris.
e. 1927 – An epidemic of Asiatic cholera was
impacting on the Punjab, and Félix d'Herelle
was able to treat 74 gravely ill patients with
his phage therapy.
f. 1940s – The Eli Lilly Company produced seven phage products for human use,
thus commercial production began. 5
Félix d'Herelle
Frederick Twort

6. REASONS FOR DECLINE
i. Fall of the Soviet Union.
ii. Subsequent displacement of its use after World War II by antibiotics.
iii. The beginning of a new era in Western countries with the golden age of antibiotics(1945).
iv. Technological limitations.
v. Inadequate scientific methodologies used by practitioners at that time.
vi. Initial problems like host range ,bacterial debris present in phage preparations & side effect.
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7. REDISCOVERY & DEVELOPMENT OF THE
FORGOTTEN CURE
1) 1980 – Phage therapy was “rediscovered” by the work of Smith and Huggins.
2) 1990s – Western phage therapy gained momentum.
3) 2000 – The field finally began maturing.
4) 2004 – Levin and Bull suggested that phage therapy only needs to decrease the numbers of
infecting bacteria to a level where the host defences can take care of the remaining bacteria.
5) Latest era of phage therapy research as well as it’s application is continuing to this day.
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8. REASON FOR REDISCOVERY
1)Antibiotic Resistance-
•Abusive use of antibiotics over the past twenty years.
•The resistance phenomenon represents an important healthcare issue.
•Return of the pre-antibiotic Era of untreatable infections and epidemics.
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9. 2)Advantages of phages over antibiotics
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Issue Phage Antibiotics
Fate of the “drug”
molecule
Exponential growth in numbers, so that the
“drug” makes more of itself at the site of
infection, where it is needed.
Metabolic destruction of the
molecule, as it works.
Concentration of the
“drug” required to kill a
given bacterium
One phage particle is sufficient to kill a
given bacterium.
Numerous molecules of the
antibiotic are needed
to kill a given bacterium.
Ability to overcome
bacterial resistance
Phages are “living” organisms that undergo
mutations, some of which can overcome
bacterial mutations.
Antibiotics are fixed & cannot
adapt to a bacterial mutation.
Bacteria that have resisted them
can pass along the resistance
trait within and between species.

10. CONTD…..
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Issue Phage Antibiotics
Spread of bacterial resistance Phages tend not to cross
species boundaries. Thus even
though the targeted bacterial
species may become resistant
to the phage, it is unlikely that
other species will.
The antibiotics in use tend to be
broad spectrum, thereby
provoking resistance in several
species and genera of bacteria.
Specificity Very specific.
Affect only the targeted bacterial
species so secondary infections
doesn't occur.
Antibiotics target both
pathogenic microorganisms and
normal microflora. Thus the the
microbial balance in the patient
is affected, which may lead to
serious secondary infections.

11.  Problem 1 - Host range
The solution
1. Screening of phages against infecting bacteria to ensure lysis.
2. Develop “multivalent” phages.
 Problem 2 - Bacterial debris present in the phage preparations
The solution
Use of modern technology for purification – centrifugation.
Problems with phage therapy and solution to overcome
the problems
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12. CONTD….
 Problem 3 - Attempts to remove host bacteria from therapeutic preparations
The solution
1. Sterile filtration
2. Titration of preparations more than once over time to ensure that the
phage remain viable if chemical are used.
 Problem 4 - Lysogeny
The solution
Use only phages that replicate using the lytic cycle.
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13. CONTD….
 Problem 5 - Anti-phage antibodies
The solution
1. Administering a higher dose of phage.
2. Study of titers of antibodies that develop in humans.
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14. USES OF PHAGE THERAPY
1. Destruction of biofilm .
2. Enzymes produced by phages used as enzybiotics.
3. In food industry for control of bacterial loads on food & to control the presence of
biofilms in the food processing environment.
4. Candidate for co-therapy with antibiotics – prevent the emergence of bacterial
resistance to antibiotic.
5. PhagoBioDerm - used to treat recurrent leg ulcer and infections in burn
victims.
6. Future application – Phage Particles as Vaccine Delivery Vehicles
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15. CONCLUSION
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The need for alternatives to antibiotics such as phage therapy is
essential due to increase of resistance of bacteria towards
antibiotics. Thus revisiting the exploitation & research on
therapeutic property of phages are needed. Though this approach
has been neglected by the western world in the past but due to
antibiotic resistance, it has been recently stressed by the WHO.
Thus knowing the history of this therapy helps us to understand
and develop it further for future use.

16. REFERENCES
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17. CONTD……
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treatment of infections (III). J Am Med Assoc 1934; 103:1934-9.
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