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Inhibition of antibiotic-induced lysis and lipopolysaccharide release from Escherichia coli 0111 :B4 by egg white lysozyme

Tokyo University of Pharmacy and Life Science. Tokyo, Japan, Institute of Chinese Materia Medica, China Academy of Traditional Chinese Medicine, Beijing, China

N. Ohno

Tokyo University of Pharmacy and Life Science. Tokyo, Japan

T. Yadomae

Tokyo University of Pharmacy and Life Science. Tokyo, Japan

Experimental and clinical data have demonstrated that antibiotics especially β-lactams, have the release of lipopolysaccarides (LPS) as adverse effects. Our previous studies showed that lysozyme (LZM) has the capacity to interact with LPS to neutralize toxicity of LPS. In this study, we examined the effect of egg white lysozyme (EW-LZM) on β-lactam-induced lysis and LPS release from Escherichia coli O111:B4. Ampicillin (ABPC) and cefotaxime (CTX) induced lysis of E. coli O111:B4 and released large amounts of LPS into culture supernatants, and thus generated excess tumor necrosis factor (TNF) from macrophages both in vitro and in vivo. Administration of EW-LZM in combination with ABPC or CTX (LZM concentration > 1 mg/ml) still showed bactericidal activity but without bacteriolysis. ABPC or CTX-induced LPS release as well as TNF productivity were significantly decreased by the presence of EW-LZM. Instability of EW-LZM/β-lactam treated cells was confirmed by the fact that: (i) the cells were easily lysed by washing in the absence of EW-LZM; and (ii) a significant amount of a periplasmic enzyme, alkaline phosphatase was detected in the culture supernatant. These results suggested that interaction of LZM with LPS protects E. coli O111:B4 from β-lactam-induced lysis and LPS release without increasing viability.

Journal of Endotoxin Research, Vol. 4, No. 2, 105-114 (1997)
DOI: 10.1177/096805199700400204


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