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

  • Kenji Kurokawa
    Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
  • Hiroshi Hamamoto
    Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
  • Miki Matsuo
    Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
  • Satoshi Nishida
    Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
  • Noriko Yamane
    Discovery Research Laboratories, Shionogi and Co., Ltd., 3-1-1 Futaba-Cho, Toyonaka, Osaka 561-0825, Japan
  • Bok Luel Lee
    National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Jangjeon-dong, Geumjeong-gu, Busan 609-735, South Korea
  • Kazuhisa Murakami
    Discovery Research Laboratories, Shionogi and Co., Ltd., 3-1-1 Futaba-Cho, Toyonaka, Osaka 561-0825, Japan
  • Hideki Maki
    Discovery Research Laboratories, Shionogi and Co., Ltd., 3-1-1 Futaba-Cho, Toyonaka, Osaka 561-0825, Japan
  • Kazuhisa Sekimizu
    Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

説明

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

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