Cyslabdan, a new potentiator of imipenem activity against methicillin-resistant Staphylococcus aureus, was isolated from the culture broth of Streptomyces sp. K04-0144 by Diaion HP-20 and ODS column chromatographies and preparative HPLC. The structure of cyslabdan was elucidated by spectroscopic analyses including NMR. The compound has a labdane-type diterpene skeleton connecting with an N-acetylcysteine via thioether linkage.Keywords cyslabdan, imipenem potentiator, methicillinresistant Staphylococcus aureus, MRSA, structural elucidation
IntroductionMethicillin-resistant Staphylococcus aureus (MRSA) is known as a major nosocomial pathogen which has also developed resistance to many other antibiotics [1]. Moreover, MRSA getting resistant to the last-resort antibiotic, vancomycin, has been reported [2,3]. These facts suggest that MRSA would acquire more resistance to vancomycin in the near future. It is therefore increasingly important and necessary to find new antimicrobial agents and to devise new measures that are effective against MRSA infection.Based on the new concept of "anti-infective drugs" developed by Ō mura [4], a screening system was established to search for microbial potentiators of imipenem activity against MRSA, and new stemphones were recently discovered from the culture broth of Aspergillus sp. FKI-2136 [5]. During our continuous screening program, an actinomycete strain K04-0144 was found to produce a strong potentiator of imipenem activity against MRSA. Activity-guided purification lead to the discovery of a novel compound designated cyslabdan (Fig. 1). From the structural elucidation, the fundamental