Mechanism of Action of New Antiinfectious Agents from Microorganisms
Currently, drug-resistant bacteria and multidrug-resistant bacteria have spread throughout the world. It is increasingly necessary to develop anti-infectives by a new approach. It is also important to elucidate new molecular targets that are responsible for microbial growth, pathogenicity, and infection. Our research group has conducted original screening systems to search for new bioactive compounds from microorganisms. During these screenings, we discovered some anti-infectives that have unique structures and biological activity. We have investigated target molecules that are involved in their mechanism of action by biochemical and genetic approach. In this study, we describe the latest findings for lariatin A, an anti-mycobacterial agent, and cyslabdan, a potentiator of β-lactam activity against methicillin-resistant Staphylococcus aureus(MRSA).
KeywordsActinomycete Strain Microbial Metabolite Lasso Peptide Attractive Drug Target Major Nosocomial Pathogen
This study was supported in part by Uehara Memorial Foundation and Kakenhi 21310146 from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. We express our thanks to Prof. Satoshi Omura and Prof. Yoko Takahashi (Kitasato University) for much help with this study, and to Dr. Yoshio Shibagaki (Kitasato University) for LC–MS/MS analysis. We also thank Dr. Makoto Matsumoto (Otsuka Pharmaceutical Co., Ltd.) for the MIC measurement of M. tuberculosis.
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