Bacteriophage therapy.

1. Bacteriophages
Dmitri Popov , PhD Radiobiology, MD (Russia).
Advanced Medical Technology and Systems Inc.
Canada.

2. Bacteriophage
Key words: bacteriophage, antibiotics, therapy, antibacterial-phage therapy,

3. Bacteriophage
Bacteriophage, dysenteri, polyvalente 1,2,3,4,6 serotypes.
Bacteriophage for therapy and prevention of dysentery.
Shigellosis, also known as bacillary dysentery or Marlow syndrome, in its most severe manifestation, is
a foodborne illness caused by infection by bacteria of the genus Shigella.
Shigellosis rarely occurs in animals other than humans
Shigella sonnae, flexneri
Shigella species are classified by four serogroups:
Serogroup A: S. dysenteriae (15 serotypes)
Serogroup B: S. flexneri (six serotypes)
Serogroup C: S. boydii (19 serotypes)
Serogroup D: S. sonnei (one serotype)

4. Bacteriophage therapy.
Groups A–C are physiologically similar; S. sonnei (group D) can be differentiated on the basis
of biochemical metabolism assays.
Three Shigella groups are the major disease-causing species: S. flexneri is the most frequently
isolated species worldwide, and accounts for 60% of cases in the developing world; S.
sonnei causes 77% of cases in the developed world, compared to only 15% of cases in the
developing world; and S. dysenteriae is usually the cause of epidemics of dysentery,
particularly in confined populations such as refugee camps.
Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary
virulence determinants. The Shigella chromosomes share most of their genes with those of E.
coli K12 strain MG1655.

5. Bacteriophage
Bacteriphage to salmonella group ABCDE
Salmonella Serogroups A,В,С,D,E.
Salmonellosis is an infection caused by Salmonella bacteria. Most people infected
with Salmonella develop diarrhea, fever, vomiting, and abdominal cramps 12 to 72
hours after infection. In most cases, the illness lasts four to seven days, and most
people recover without treatment. In some cases, the diarrhea may be so severe that
the patient becomes dangerously dehydrated and must be hospitalized.
Salmonellosis is a major cause of bacterial enteric illness in both humans and animals.
Each year an estimated 1.4 million cases of salmonellosis occur among humans in the
United States.
www.researchgate.net850 × 608Search by image Figure 1. General overview of the
current classification of Salmonella enterica . doi:10.1371/journal.ppat.1002776.g001

6. Bacteriophage

7. Bacteriophage
Bacteriophage to Salmonella enterica typhi.
Therapy and prophylaxis.
Worldwide, typhoid fever affects roughly 17 million people annually, causing nearly 600,000 deaths. The
causative agent, Salmonella enterica typhi (referred to as Salmonella typhi.
Infection of S. typhi leads to the development of typhoid, or enteric fever. This disease is characterized by
the sudden onset of a sustained and systemic fever, severe headache, nausea.
Other symptoms include constipation or diarrhea, enlargement of the spleen, possible development of
meningitis, and/or general malaise.
Untreated typhoid fever cases result in mortality rates ranging from 12-30% while treated cases allow for
99% survival.
http://web.uconn.edu/mcbstaff/graf/Student%20presentations/Salmonellatyphi/Salmonellatyphi.html

8. Bacteriophage
Bacteriophage to Stapyilococcus aureus.
Staphylococcus aureus is a gram-positive coccal bacterium that is a member of the Firmicutes,
and is frequently found in the nose,respiratory tract, and on the skin. It is often positive
for catalase and nitrate reduction. Although S. aureus is not always pathogenic, it is a
common cause of skin infections such as abscesses, respiratory infections such as sinusitis,
and food poisoning. Pathogenic strains often promote infections by producing
potent protein toxins, and expressing cell-surface proteins that bind and inactivate
antibodies. The emergence of antibiotic-resistant strains of S. aureus such as methicillin-
resistant S. aureus (MRSA) is a worldwide problem in clinical medicine.
https://en.wikipedia.org/wiki/Staphylococcus_aureus
https://www.google.ca/search?q=staphylococcus+classification&espv

9. Bacteriophage to staphylococcus.

10. Bacteriophage to staphylococcus.
Staphylococcus can cause a wide variety of diseases in humans and animals through
either toxin production or penetration. Staphylococcal toxins are a common cause of
food poisoning, for they can be produced by bacteria growing in improperly stored
food items. The most common sialadenitis is caused by staphylococci, as bacterial
infections.
Bacteriophage to staph infections
Treatment and prevention of purulent infections of the skin , mucous membranes,
coagulase-negative staphylococci caused by staphylococci , as well as dysbacteriosis.
Bacteriophage is used to treat cystitis , cholecystitis , acute tonsillitis , enterocolitis ,
and others .

11. Bacteriophage
Бактериофаг. Bacteriophage to Streptococcus, Enterococcus.
https://www.google.ca/imgres?imgurl=https://upload.wikimedia.org/wikipedia

12. Streptococcus infections.

13. Streptococcus classification.

14. Bacteriophage
Bacteriophage to Echerechia coli.
Бактериофаг коли,
Энтеропатогенная Echerichia coli.
Escherichia coli (/ˌɛʃəˈrɪkiə ˈkoʊlɪ/ Anglicized to /ˌɛʃəˈrɪkiə ˈkoʊlaɪ/; commonly abbreviated E.
coli) is a gram-negative, rod-shapedbacterium that is commonly found in the
lower intestine of warm-blooded organisms (endotherms).
Most E. coli strains are harmless, but some serotypes are pathogenic and can cause serious
infections or food poisoning in humans, and are occasionally responsible for product
recalls

15. Bacteriophage.
Phage therapy—viruses that specifically target pathogenic bacteria—has been
developed over the last 80 years, primarily in the former Soviet Union, where it was
used to prevent diarrhea caused by E. coli.
Presently, phage therapy for humans is available only at the Phage Therapy Center in
the Republic of Georgia and in Poland.
However, on January 2, 2007, the United States FDA gave Omnilytics approval to
apply its E. coli O157:H7 killing phage in a mist, spray or wash on live animals that will
be slaughtered for human consumption.
The enterobacteria phage T4, a highly studied phage, targets E. coli for infection.

16. Bacteriophage.
E.coli infections:
Pathogenic E.coli strains can be categorized based on elements that can elicit an
immune response in animals, namely:
O antigen: part of lipopolysaccharide layer
K antigen: capsule
H antigen: flagellin
For example, E.coli strain EDL933 is of the O157:H7 group

17. Bacteriophage therapy.
Enterotoxigenic E. coli (ETEC)
causative agent of diarrhea (without fever) in humans, pigs, sheep, goats, cattle, dogs, and horses.
ETEC uses fimbrial adhesins (projections from the bacterial cell surface) to bind enterocyte cells in
the small intestine. ETEC can produce two proteinaceous enterotoxins: The larger of the two
proteins, LT enterotoxin, is similar to cholera toxin in structure and function.
The smaller protein, ST enterotoxin causes cGMP accumulation in the target cells and a subsequent
secretion of fluid and electrolytes into the intestinal lumen.
ETEC strains are non-invasive, and they do not leave the intestinal lumen. ETEC is the leading bacterial
cause of diarrhea in children in the developing world, as well as the most common cause of traveler's
diarrhea. Each year, ETEC causes more than 200 million cases of diarrhea and 380,000 deaths, mostly
in children in developing countries.
https://en.wikipedia.org/wiki/Pathogenic_Escherichia_coli#Serotypes

18. Bacteriophage therapy.
Enteropathogenic E. coli (EPEC) , causative agent of diarrhea in humans, rabbits, dogs,
cats and horses.
Like ETEC, EPEC also causes diarrhea, but the molecular mechanisms of colonization
and aetiology are different. EPEC lack ST and LT toxins, but they use an adhesin known
as intimin to bind host intestinal cells. This virotype has an array of virulence factors
that are similar to those found in Shigella, and may possess a shiga toxin. Adherence
to the intestinal mucosa causes a rearrangement ofactin in the host cell, causing
significant deformation. EPEC cells are moderately invasive (i.e. they enter host cells)
and elicit an inflammatory response. Changes in intestinal cell ultrastructure due to
"attachment and effacement" is likely the prime cause of diarrhea in those afflicted
with EPEC. https://en.wikipedia.org/wiki/Pathogenic_Escherichia_coli#Serotypes

19. Bacteriophage therapy.
Enteroinvasive E. coli (EIEC) . EIEC infection causes a syndrome that is identical
to shigellosis, with profuse diarrhea and high fever.
The most infamous member of this virotype is strain O157:H7, which causes bloody
diarrhea and no fever. EHEC can cause hemolytic-uremic syndrome and sudden
kidney failure. It uses bacterial fimbriae for attachment (E. coli common pilus, ECP),is
moderately invasive and possesses a phage-encoded shiga toxin that can elicit an
intense inflammatory response.
https://en.wikipedia.org/wiki/Pathogenic_Escherichia_coli#Serotypes

20. Bacteriophage therapy.
Enteroaggregative E. coli (EAEC)
so named because they have fimbriae which aggregate tissue culture cells, EAEC bind
to the intestinal mucosa to cause watery diarrhea without fever. EAEC are non-
invasive. They produce a hemolysin and an ST enterotoxin similar to that of ETEC.

21. Bacteriophage therapy
Adherent-Invasive E. coli (AIEC)
AIEC are able to invade intestinal epithelial cells and replicate intracellularly. It is likely
that AIEC are able to proliferate more effectively in hosts with defective innate
immunity. They are associated with the ileal mucosa in Crohn's disease.
https://en.wikipedia.org/wiki/Pathogenic_Escherichia_coli#Serotypes

22. Bacteriophage therapy.
Enterohemorrhagic E. coli (EHEC) .
The most infamous member of this virotype is strain O157:H7, which causes bloody
diarrhea and no fever. EHEC can cause hemolytic-uremic syndrome and sudden
kidney failure. It uses bacterial fimbriae for attachment (E. coli common pilus,
ECP),[19] is moderately invasive and possesses a phage-encoded shiga toxin that can
elicit an intense inflammatory response.

23. Bacteriophage
Bacteriophage to Pseudomonas aeruginosa.
Pseudomonas aeruginosa is a common Gram-negative, rod-shaped bacterium that
can cause disease in plants and animals, including humans.
A species of considerable medical importance, P. aeruginosa is a prototypical
"multidrug resistant (MDR) pathogen" recognised for its ubiquity, its intrinsically
advanced antibiotic resistance mechanisms, and its association with serious illnesses
– especially nosocomial infections such as ventilator-associated pneumonia and
various sepsis syndromes.

24. Bacteriophage
Bacteriophage to Klebsiella pneumoniae.
Klebsiella pneumoniae is a Gram-negative, nonmotile, encapsulated, lactose-
fermenting, facultative anaerobic, rod- shapedbacterium.
Klebsiella appears as a mucoid lactose fermenter on MacConkey agar.
Although found in the normal flora of the mouth, skin, and intestines, it can cause
destructive changes to human and animal lungs if aspirated (inhaled), specifically to
the alveoli (in the lungs) resulting in bloody sputum. In the clinical setting, it is the
most significant member of the Klebsiella genus of Enterobacteriaceae. K.
oxytoca and K. rhinoscleromatis have also been demonstrated in human clinical
specimens. In recent years, Klebsiella species have become important pathogens
in nosocomial infections.

25. Bacteriophage
Bacteriophage to Klebsiella, polyvalent.
Klebsiella rhinoscleromatis, Klebsiell pneumoniae.

26. Bacteriophage
Pyo-bacteriophage, polyvalent,mixt.
P. aeruginosa, P. mirabilis, vulgaris,
K. pneumoniae, Staphylococcus, Enterococcus, E. coli (enteropatogenic)

27. Bacteriophage
Pyo bacteriophage, complex (Секстафаг)
Bacteriophage to P. aeruginosa, P. mirabilis, P. vulgaris,
K. pneumoniae, Staphylococcus, Enterococcus,
энтеропатогенная E. coli, K. oxytoca

28. Literature
BACTERIOPHAGE BASED PREPARATIONS: A BRIEF SURVEY OF CURRENT STATE
AND FUTURE DEVELOPMENT
I.V. Krasilnikov, K.A. Lysko, E.V. Otrashevskaya, A.K. Lobastova
Federal State Unitary Company ”Microgen” Scientific Industrial Company for
Immunobiological Medicines” of the Ministry of Health and
Social Development of the Russian Federation, Moscow

29. Literature
Wright, C.H. Hawkins et al. A controlled clinical trial of a
therapeutic bacteriophage preparation in chronic otitis due to
antibiotic-resistant Pseudomonas aeruginosa; a preliminary
report of efficacy // Clinical Otolaryngology. – 2009. – Vol. 34,
Issue 4. – Р. 349–357.
Ackermann H. – W., Dubow M. S.
Viruses of prokaryotes, vol. I. General properties of bacteriophages. – CRC
Press: Boca Raton, 1987. 231 p.

30. Literature
Weber-Dabrowska, Zimecki M., Kruzel M. et al. Alternative
therapies in antibiotic-resistant infection // Advances in Medical
Sciences. – 2006. – Vol. 51. – P. 242–244.
Abedon, S. T. (1994). Lysis and the Interaction between Free Phages and Infected
Cells, p. 397-405. In J. D. Karam (ed.), Molecular Biology of Bacteriophage T4.
American Society for Microbiology, Washington, DC.

31. Literature
Barrow, P. A. and J. S. Soothill. (1997). Bacteriophage Therapy and Prophylaxis:
rediscovery and renewed assessment of the potential. Trends Microbiol 5:268-271
Burnet, F. and M. McKie (1929). Observations on a permanently lysogenic strain of B.
enteridis gaerther. Austral. J. Exptl. Biol. Med. Sci. 6: 277-284.]

32. Literature
Doermann, A. D. (1948). Lysis and lysis inhibition with Escherichia coli bacteriophage.
J. Bacteriol. 55:257-275.
Bacteriophage Therapy
Alexander Sulakvelidze,,* Zemphira Alavidze,and J. Glenn Morris, Jr.
Antimicrob Agents Chemother. 2001 Mar; 45(3): 649–659.
doi: 10.1128/AAC.45.3.649-659.2001

33. Literature
Samsygina, G. A., and E. G. Boni. 1984. Bacteriophages and phage therapy in pediatric
practice. Pediatria 4:67–70.
Schless, R. A. 1932. Staphylococcus aureus meningitis: treatment with specific
bacteriophage. Am. J. Dis. Child. 44:813–822

34. Literature
Peremitina, L. D., E. A. Berillo, and A. G. Khvoles. 1981. Experience in the therapeutic
use of bacteriophage preparations in suppurative surgical infections. Zh. Mikrobiol.
Epidemiol. Immunobiol. 9:109–110
Chopra, I., J. Hodgson, B. Metcalf, and G. Poste. 1997. The search for antimicrobial
agents effective against bacteria resistant to multiple antibiotics. Antimicrob. Agents
Chemother. 41:497–503.
Eaton, M. D., and S. Bayne-Jones. 1934. Bacteriophage therapy. Review of the
principles and results of the use of bacteriophage in the treatment of infections.
JAMA 23:1769–1939

35. Literature
Schless, R. A. 1932. Staphylococcus aureus meningitis: treatment with specific
bacteriophage. Am. J. Dis. Child. 44:813–822
Slopek, S., A. Kucharewicz-Krukowska, B. Weber-Dabrowska, and M. Dabrowski. 1985.
Results of bacteriophage treatment of suppurative bacterial infections. VI. Analysis of
treatment of suppurative staphylococcal infections. Arch. Immunol. Ther. Exp.
33:261–273.
Smith, H. W., and M. B. Huggins. 1987. The control of experimental E. coli diarrhea in
calves by means of bacteriophage. J. Gen. Microbiol. 133:1111– 1126

36. Literature
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clinical microbiology, 7th ed. American Society for Microbiology, Washington, D.C.
Zhukov-Verezhnikov, N. N., L. D. Peremitina, E. A. Berillo, V. P. Komissarov, V. M.
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37. Literature
MICROBIOLOGIcAL REVIEWS, Sept. 1992, p. 430-481 Vol. 56, No. 3
0146-0749/92/030430-52$02.00/0
Copyright © 1992, American Society for MicrobiologY.
RY YOUNG
Department of Biochemistry and Biophysics, Texas A&M University, College Station,
Texas 77843

38. Literature