We are approaching a time where antimicrobial drugs may no longer be effective due to the growing global antimicrobial resistance crisis, coupled with the lack of antimicrobial drug discovery and development. New antimicrobial therapies are needed, and endophytes from marine macroalgae have been highlighted as an important biological reservoir for the identification of novel antimicrobial molecules. A preliminary investigation of marine macroalgae from the Bay of Fundy, New Brunswick, Canada for their endophytes indicated this location to be an excellent source of endophytic fungi possessing antimicrobial activity. One hundred and forty fungal endophytes were isolated from 20 species of marine macroalgae collected from the Bay of Fundy. Fifty-four endophytes were identified to the genus or species level, and include eleven fungi not previously isolated as endophytes of marine macroalgae. The identity of 86 isolates could not be confirmed through DNA sequencing due to an inability to amplify or sequence DNA or due to low sequence homology with entries in GenBank. These isolates were designated codes according to their morphology. Each endophyte was fermented to obtain an extract in order to facilitate the discovery of new natural products. In order to prioritise the extracts obtained from these endophytic fungi, an antimicrobial bioactivity profiling technique was developed using nine microorganisms and a panel of 17 antimicrobial standards to not only attempt to identify new antimicrobial natural products, but also those that possess unique antimicrobial targets or modes of action. Principal component analysis of the extract bioactivity profiles revealed that the profiles of 37 extracts were unique within the library. Hierarchical cluster analysis using the profiles of the 37 unique extracts and the 17 antimicrobial standards showed that 26 extracts possessed bioactivity profiles that were distinct from the antimicrobial standards and thus warranted further investigation. Subsequent bioassay guided fractionation of four fungal extracts led to the isolation of six antimicrobial natural products: penicillic acid, methylenolactocin, fumagillin, fumigatin oxide, poly(3R,5R-dihydroxyhexanoic acid) and (P/M)-maximiscin. These natural products, while being known chemical entities, are all reported to possess antimicrobial activity and may play an important role in future antimicrobial drug discovery and development.
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