Evaluation of Target Specificity of Antibacterial Agents Using Staphylococcus aureus ddlA Mutants and d -Cycloserine in a Silkworm Infection Model

Author:

Kurokawa Kenji12,Hamamoto Hiroshi1,Matsuo Miki1,Nishida Satoshi1,Yamane Noriko3,Lee Bok Luel2,Murakami Kazuhisa3,Maki Hideki3,Sekimizu Kazuhisa1

Affiliation:

1. Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

2. National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Jangjeon-dong, Geumjeong-gu, Busan 609-735, South Korea

3. Discovery Research Laboratories, Shionogi and Co., Ltd., 3-1-1 Futaba-Cho, Toyonaka, Osaka 561-0825, Japan

Abstract

ABSTRACT The availability of a silkworm larva infection model to evaluate the therapeutic effectiveness of antibiotics was examined. The 50% effective doses (ED 50 ) of d -cycloserine against the Staphylococcus aureus ddlA mutant-mediated killing of larvae were remarkably lower than those against the parental strain-mediated killing of larvae. Changes in MICs and ED 50 of other antibiotics were negligible, suggesting that these alterations are d -cycloserine selective. Therefore, this model is useful for selecting desired compounds based on their therapeutic effectiveness during antibiotic development.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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