PMB: Bacteriophages 8

Question 1

What are bacteriophages and what can they be used for?

Answer 1

• Viruses that infect bacteria
• Used for staphylococcal skin infections and dysentery
• Still used in some East Eueopen countries

Question 2

What can be said about phages modes of actions?

What are they also referred to as

Answer 2

obligate intracellular parasites which are highly host specific. E.g E.coli Tphages

Each phage has a very specific mchanism of action, which gives each ohage high specificty

Question 3

Why are AB of more use than Phages?

Answer 3

AB have a more generic mechanism of action which allows more species to be targeted at once

Question 4

What are issues for phage therpay?

Answer 4

1. They targte a very narrow range of oraganisms
2. They may not always be lytic, they may enter the lysogenic cycle and become less effective. If they enter the lysogenic cycle they have the potential to introduce enhance virulence or AB resistance e.g. necrotising fasciitis
3. Treatment requires prior information about the organism
4. The phage used in medication must be pure
5. Formulation can be probalamtic
6. Must consider the PK, however this is complicated due to the self replicating nature of the phages
7. Phages can be distributed around the body so could evoke an immune response which cpuld possibly lead to them being inactivated by the hosts ABs
   8.

Question 5

When were phages approved and licenced?

Answer 5

• 2006 lincenced as FDA
• Product composed of 6 phages and is used for listeria monocytogen
• Used as a spray for raw meats and for listeriosis

Question 6

How are lytic phages released from host cells?

Answer 6

Cells need to bust open and and then the cell wall degrade on lysis

Question 7

What is endolysin?

Answer 7

The process by where phage peptidoglycan hydrolases degrade the cell wall

Question 8

What types of phage endolysins is there?

Answer 8

• Different classes each have different cataklytic activity i.e cleave different bonds in the stucture

Question 9

What is the peptidoglycan layer consit off?

Answer 9

Made of:

• 2 Glucose derviatives: NAG and NAM joined by glycosidic bonds
• 4 AAs: D and L - alanine, Glutamic acid and DAP/lysine koined by peptide bonds

This forms the repeating unit glycan tetrapeptide

Question 10

What are endolysins?

Answer 10

single polypeptide consiting of 2 domains:

1. A PG binding domain which provides specificity
2. a catlaytic domain which cleaves PG

Question 11

Therpautic uses?

Answer 11

• Certain types can act synergistically
• e.g. Streptococcus pneumoniae Cpl-1 and Pal.
• Could be possible to produce single hybrid endolysin that has enhanced activity
• mostly used fot Grame POsitives due to LPS in gram negative

Question 12

Preclinical trials/ prodycts

Answer 12

Added to Staph. aureus (Gram +ve) in vitro lysis occurred instantly

Limited potential for development of resistance

In vivo study with mouse injected with Bacillus cereus (Gram +ve) via intraperitoneal (into body cavity) route

Simultaneous endolysin treatment cured mice

Shown to increase effectiveness of some antibiotic therapy through re-sensitisation e.g. β lactams

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