title: Physicochemical characterization of the staphylolytic LysK enzyme in complexes with polycationic polymers as a potent antimicrobial.
abstract: Staphylococcus aureus causes many serious visceral, skin, and respiratory diseases. About 90% of its 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, and 55.2 kDa and their block copolymers with polyethylene glycol PLL10-PEG114, PLL30-PEG114, and PLL30-PEG23) as a basis for creating active and stable antimicrobial. Complexing with polycationic PLLs produces a stabilizing effect on LysK due to structure ordering in its molecules and break-down of aggregates as a result of electrostatic interaction. The stability of LysK in the presence of PLL-PEG block copolymers improves by both electrostatic and hydrophobic mechanisms. Complexes of LysK with 2.5, 9.6, 55.2 kDa poly-l-lysines and PLL30-PEG114 have demonstrated sufficient stability at the temperatures of physiological activity (37 °C) and storage (4 °C and 22 °C).
authors.affiliation: Department of Chemical Enzymology, Faculty of Chemistry, M.V. Lomonosov Moscow State University, Vorobievy Gory, 1-11, Moscow 119991, Russia. luboff.filatova@gmail.com
authors.forename: Lyubov Y
authors.initials: LY
authors.lastname: Filatova
authors.forename: David M
authors.initials: DM
authors.lastname: Donovan
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Becker
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Lebedev
authors.forename: Anastasia D
authors.initials: AD
authors.lastname: Priyma
authors.forename: Helena V
authors.initials: HV
authors.lastname: Koudriachova
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Klyachko
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D055598:Chemical Phenomena; D015195:Drug Design; D010450:Endopeptidases / Q000737:chemistry* / Q000494:pharmacology*; D004795:Enzyme Stability; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000166:cytology* / Q000187:drug effects*; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents; D011108:Polymers; D010450:Endopeptidases; C001143:endolysin
keywords: A(600); Antibacterial enzymes; DLS; FTIR; Fourier-transform infrared spectroscopy; LMW; MRSA; PLL; PLL(x)–PEG(y); Polycation; Stability; Stabilization; Staphylococcal infections; dynamic light scattering; half-inactivation time; low molecular weight; methicillin-resistant Staphylococcus aureus; optical density at 600 nm; poly-l-lysine hydrobromide; poly-l-lysine hydrobromide–polyethylene glycol block copolymer, x and y values correspond to a number of l-lysine and ethylene glycol structural units; τ(1/2)