Antimicrobial Activity in Secondary Metabolites

The search for novel classes of antimicrobial compounds is a critical strategy in addressing the emergence of antimi-crobial resistance in medically important infections[9,17]. For example,vancomycin is the antibiotic of choice for treating MRSA infections;however,the drug is renally toxic requiring constant dose monitoring and its effec-tiveness is being potentially compromised by the emer-gence of vancomycin-resistant enterococci[3,41]. Similarly,amphotericin B,which is often the only effective antimycotic for treatment of systemic fungal infections (including C.albicans)is similarly limited due to severe infusion-related nephrotoxicity and numerous other side effects[25].Consequently,we have explored the under exploited genus Preussia for potential drug development. Interest in examining endophytic species as a source of novel antimicrobial natural products has been heightened by reports which have shown that when endophyte-colon-ised plants are challenged by microbial pathogens they activate host defences more ef?ciently than non-symbiotic plants[29,33,34].As indicated above,initial antimicrobial activity was demonstrated for13/18Preussia isolates.The activity of EtOAc extracts in eight of these isolates indi-cated that some of the bioactive compounds are lipid sol-uble and more speci?cally,HPLC fractions contained secondary metabolites that inhibited the growth of MRSA and/or C.albicans.Interestingly,isolates that had similar ITS regions showed differing bioactivity.In particular, isolate ADM2.11was found to have a99%sequence similarity over350bp with NVM2.5.However,when these isolates were tested for bioactivity,sample ADM2.11 showed both antifungal and antibacterial activity whilst NVM2.5did not.Variable Preussia isolate biochemistry has been described by Peterson et al.[30],who found that the two P.africana isolates produced such differing enzymatic activity that it was suggested they were poten-tially different species.However,differing antimicrobial activity among isolates of the same species has not been previously reported for the genus Preussia,although they have been reported for many other fungal species[26,31]. The observance of several isolates that showed either a loss or gain of bioactivity at the HPLC stage is most likely due to concentration issues when testing fractions.Of particular interest was the bioactivity present in HPLC fractions from isolate BSH2.9(Preussia aff.africana).Fractions col-lected at3,4and5min each contained mixtures of com-pounds that inhibited MRSA.Thus far our chemical investigations have suggested the presence of at least six new compounds in these bioactive fractions.Additional HPLC work is currently underway in an attempt to purify all these new compounds.Acknowledgments Rachel Mapperson is supported by an Austra-lian Postgraduate award.

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