TD: Endolysins

Question 1

What are endolysins? What are they produced by? What is their function?

Answer 1

The genomes of many bacteriophages are encoded for the production of lysins, highly evolved peptidoglycan-degrading enzymes which allow the phage to escape from the bacterial cell during the phage lytic cycle

Endolysins can also cause lysis when applied exogenously.

Question 2

What are useful characterisitics of endolysins?

Answer 2

• Endolysins evolved along with bacteria over billions of years and they select bacterial target sites that don’t change as a result of mutation….i.e. highly conserved chemical bonds. This limits the opportunity for resistance developing and it has not been observed even with repeat exposure.……although the threat of resistance arising can never be ruled out with any new treatment.
• Endolysins active against Gram +ve bacteria have evolved a modular structure, often with multiple lytic and cell wall-binding domains.
  • Specific cell binding domains - more specific to bacteria
• Modular structure – potentially allows protein engineering to be
• Rapid lysis limits the potential for the development of resistance.
• Because of the specificity of action, beneficial commensal bacteria are not killed, reducing the chance of related side-effects and opportunistic infection following treatment (often seen after courses of antibiotics).

used to alter the host spectrum.

• Sub-units could potentially be rearranged between endolysins to create novel enzymes with optimised functionality.
• Mutagenesis has been used to alter solubility and thermal stability of an endolysin.

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Question 3

Application of endolysisns

Answer 3

Researchers are mainly targeting Gram positive pathogens because the outer membrane of Gram negative bacteria largely protects their peptidoglycan from endolysin action.

Modifying endolysins with polyethylene glycol can be used to improve their half-life when used systemically.

Question 4

Endolysin products?

Answer 4

StaphefektTM is an endolysin product for treating acne and eczema

Question 5

Barriers to development

Answer 5

There is a lack of technology for the cost-effective scale-up of endolysin production.

Regulatory pathways also need to be established.