Bacteriophage: History & Modern Applications of Virus Alternatives to Antibiotics, Assignments of Microbiology

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Bacteriophage

Replacing Antibiotic

Therapy

Antibiotic (anti-bacterial)

A type of antimicrobial drug. Used in the treatment and prevention of bacterial infections. Kill or inhibit the growth of bacteria.

Antibiotics work?

# A Bactericidal antibiotic kills the bacteria generally by

either interfering with the formation of the bacterium's cell

wall or its cell contents. Penicillin, daptomycin,

fluoroquinolones, metronidazole, nitrofurantoin and co-

trimoxazole are some example of Bactericidal antibiotics.

# A

Bacteriostatic antibiotic stops bacteria from multiplying by

interfering with bacterial protein production, DNA

replication, or other aspects of bacterial cellular

metabolism. Some Bacteriostatic antibiotics are

tetracyclines, sulphonamides, spectinomycin, trimethoprim,

chloramphenicol, macrolides and lincosamides.

Mechanism of Antibiotic Resistance

*Drug inactivation due to enzyme modification.

*Alternation of target

site. *Alternation of metabolic

pathway. *Reduce drug

accumulation. *Bio-film

formation.

*Restricted penetration of antibiotics.

*Adaptive response.

*Quorum sensing.

*Genetic alternation to persister cell.

*Nutritent limitations altered microenvironment.

Bacteriophage

Discovery / History of

Bacteriophage

In 1896 Ernest hanbury hankin, British

bacteriologist found bacteriophage in ganges & yamuna rivers in india. They pass theough a very fine porcealin filter & was heat labile. Presence of marked antibacterial activity against vibro c holerae, which he observed in the waters.

In 1915 - Frederick twort

& In 1917 Felix d’herellein both scientists discovered bacteriophage independently.

Phage location? #Human and animal intestine. #Bunning water. #Soil. #Effluent outlets. #Sewage from corpses.

Classification/ Taxonomy

By International Committee on Taxonomy of Viruses(ICTV): 3-order, 73-families, 9-subfamilies, 287-genera & 1938 virus species.

Bacteriophages as an intervention?

#Felix d’Herelle explored using phage solutions to treat

dysentery in humans.

#During World war II phage solutions were supplied to soviet

union & russian soldiers, where it was used to prevent

diarrhea caused by E.coli.

#Republic of Georgia has been using phage therapy since the

1940s.

#Present phage therapy for humans is available at the phage

therapy centre in the Republic of Georgia & in poland.

#In 2006,US

FDA approved Listeria phage solution for using in ready-to-eat

meat & poultry. #In

2011,US FDA approved Ecoli phage for using on food.

Lifecycle: Lytic cycle Vs Lysogenic Cycle

Why Phage Therapy?

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.

Issue Phage Antibiotics 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 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