Interactions of a lysozyme-monomethoxypolyethylene glycol conjugate with lipopolysaccharides and lipid bilayers and effects of conjugate on gram-negative bacteria.
We have been studying a lysozyme derivative, called mPEG-lysozyme, in which Lys 33 is bound with a monomethoxypolyethylene glycol derivative. Here, we examined the surface hydrophobicity of the derivative and also its interactions with lipopolysaccharides and lipid bilayers. These properties may affect the antimicrobial activity of mPEG-lysozyme toward Gram-negative microorganisms. The lysozyme derivative had more than 150% of the antimicrobial activity for such microorganisms with that of native lysozyme taken to be 100%. Spectroscopic analyses indicated that mPEG-lysozyme bound to lipopolysaccharides with higher affinity than lysozyme, because of the high surface hydrophobicity of the derivative. In an experiment on carboxyfluorescein-leakage, mPEG-lysozyme strongly interacted with liposomes constructed from phosphatidylcholine, releasing carboxyfluorescein from the liposomes more effectively than lysozyme did. mPEG-lysozyme may perturb the outer membrane of Gram-negative microorganisms, gaining itself access to the peptidoglycan layers of the bacterium.
Nodake
Yuichi
Y
Division of Bioresource and Bioenvironmental Sciences, Graduate School of Kyushu University, Fukuoka, Japan. nodake@spring8.or.jp
Iwasaki
Kenta
K
Yamasaki
Nobuyuki
N
D001412:Bacillus subtilis / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects*; D005452:Fluoresceins / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013050:Spectrometry, Fluorescence; D013499:Surface Properties
D005452:Fluoresceins; D008051:Lipid Bilayers; D008070:Lipopolysaccharides; C024098:6-carboxyfluorescein; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D009113:Muramidase