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Journal of Antimicrobial Chemotherapy (1987) 20, 37-45
© 1987 The British Society for Antimicrobial Chemotherapy

research-article

Effect of a diazaborine derivative (Sa 84.474) on the virulence of Escherichia coli

Charles Lam, Friederike Turnowsky, Gregor Högenauer and E. Schütze

Sandoz Forschungsinstitut Brunner Straße 59 A-1235 Vienna, Austria

accepted 29 December 1986

The scope of selective inhibition of lipopolysaccharide (LPS) biosynthesis in virulent organisms with a diazaborine derivative (Sa 84.474) as a means to render them avirulent was explored. A serum resistant Escherichia coli 0111:B4 became serum sensitive following its cultivation in vitro in media containing 1.5 mg/1 of Sa 84.474, a concentration shown previously to inhibit over 95% of normal LPS biosynthesis in its mutant J5 strain. An encapsulated E.coli 01:K1 was also converted to serum sensitivity. In addition, Sa 84.474-pretrcatment increased the efficiency with which the previously resistant organisms were opsonized in normal human serum and subsequently phagocytosed by granulocytes. In vivo, intravenously inoculated, Sa 84.474-pretreated bacteria were rapidly removed from the blood circulation and were significantly (P <005) less virulent in inducing lethal peritoneal infections in mice (LD504.9±l x 106cfu) when compared to untreated control bacteria (LD50 2.2 ±0.97 x 106 cfu). The results suggest that the LPS plays an important role in the virulence of the two bacterial strains and imply that agents acting in a similar manner but with acceptable selective toxicity might be novel drugs for therapy of Gram-negative bacterial infections.


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