Title: Physicochemical characterization of Staphylococcus aureus-lysing LysK enzyme in complexes with polycationic Authors
|Filatova, Lubov -|
|Becker, Stephen -|
|Lebedev, Dmitry -|
|Priyma, Anastasiya -|
|Koudriachova, Elena -|
|Kabanov, Alexander -|
|Klyachko, Natalia -|
Submitted to: Biochimie
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 24, 2013
Publication Date: May 1, 2013
Citation: Filatova, L.Y., Donovan, D.M., Becker, S.C., Lebedev, D.N., Priyma, A.D., Koudriachova, E.V., Kabanov, A.V., Klyachko, N.L. 2013. Physicochemical characterization of Staphylococcus aureus-lysing LysK enzyme in complexes with polycationic. Biochimie. Interpretive Summary: Background: Novel antimicrobials against multi-drug resistant Staphylococcus aureus are much needed. One candidate antimicrobial enzyme is LysK, a bacteriophage enzyme that kills staphylococci by digesting the cell wall and causing the pathogen to lyse. LysK is sensitive to harsh environments. This work examines the use of organic polymers to help stabilize the enzyme under sub optimal conditions that the enzyme might face when used as an antimicrobial. Results: Numerous combinations of organic polymers were identified that could help stabilize the activity of LysK under harsh conditions. Conclusion: Having identified organic polymers that help stabilize LysK, the opportunity is now available to test LysK in complexes with these organics for the improved ability to fight staphylococcal infections in animal models.
Technical Abstract: Staphylococcus aureus causes many serious visceral, skin, and respiratory diseases. About 90% of clinical strains are multi-drug resistant, but the use of bacteriophage lytic enzymes offers a viable alternative to antibiotic therapy. LysK, the phage K endolysin can lyse S. aureus when purified and exposed externally. It has been investigated in its complexes with polycationic polymers (poly-L-lysines (PLLs) of molecular weights 2.5, 9.6 55.2 kDa and their block-copolymers with polyethylene glycol PLL10-PEG114, PLL30-PEG114, and PLL30-PEG32) as a basis for creating and active and stable antimicrobial. Complexing with polycationic PLLs produces a stabilizing effect on LysK, presumably due to structure ordering, break-down of aggregates through electrostatic and hydrophobic interactions. Complexes of LysK with 2.5, 9.6, 55.2 kDa PLLs and PLL30-PEG114 have demonstrated increased stability at the temperatures of physiological activity (37°C) and storage (4ºC and 22°C).