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Antimicrobial Agents and Chemotherapy, September 2009, p. 4025-4027, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00200-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Evaluation of Target Specificity of Antibacterial Agents Using Staphylococcus aureus ddlA Mutants and D-Cycloserine in a Silkworm Infection Model{triangledown}

Kenji Kurokawa,1,2* Hiroshi Hamamoto,1 Miki Matsuo,1,{dagger} Satoshi Nishida,1,{ddagger} Noriko Yamane,3 Bok Luel Lee,2 Kazuhisa Murakami,3,§ Hideki Maki,3 and Kazuhisa Sekimizu1

Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan,1 National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Jangjeon-dong, Geumjeong-gu, Busan 609-735, South Korea,2 Discovery Research Laboratories, Shionogi and Co., Ltd., 3-1-1 Futaba-Cho, Toyonaka, Osaka 561-0825, Japan3

Received 13 February 2009/ Returned for modification 12 March 2009/ Accepted 10 June 2009

The availability of a silkworm larva infection model to evaluate the therapeutic effectiveness of antibiotics was examined. The 50% effective doses (ED50) 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 ED50 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.

* Corresponding author. Mailing address: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Phone: 81-3-5841-4821. Fax: 81-3-5684-2973. E-mail: kurokawa{at}mol.f.u-tokyo.ac.jp

{triangledown} Published ahead of print on 22 June 2009.

{dagger} Present address: Department of Bacteriology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

{ddagger} Present address: Department of Chemistry, The University of Chicago, Chicago, IL 60637.

§ Present address: Genome Pharmaceuticals Institute Co. Ltd., The University of Tokyo Entrepreneur Plaza, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Antimicrobial Agents and Chemotherapy, September 2009, p. 4025-4027, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00200-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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