Warding Off Disease on Coral Reefs: Antifungal Chemical Cues in Tropical Seaweeds

Unlike many animals, seaweeds do not possess inducible immune systems to ward off disease.  In many cases, they produce small molecules – natural antibiotics – that prevent colonization or infection by pathogens.  We have found that seaweeds produce unusual secondary metabolites against pathogen attack, including complex polyketides and terpene-shikimate macrolides not seen in any other organisms.  Surprisingly, these natural antifungals are not distributed evenly across algal surfaces; instead they are concentrated at discrete surface patches where they provide bursts of protection at sites that may be especially vulnerable to infection due to prior wounding.  In collaboration with the Fernandez lab at Georgia Tech, we applied surface imaging mass spectrometry to intact algal surfaces to show that antifungal defenses are heterogeneously distributed, with compound concentrations high enough at localized patches to block infection.  This patchy distribution may represent an optimal defense strategy, in which the most vulnerable parts of the alga are best defended.  Chemical defenses of seaweeds may also serve as valuable leads for pharmaceutical development.  Members of one group of algal antifungal agents, the bromophycolides, exhibit potent antimalarial activity with an unexpected mechanism of action, inhibiting growth of the malarial parasite Plasmodium falciparum at sub-micromolar concentrations.  Using a molecular probe designed from the seaweed’s antifungal agent, we identified the molecular target and drug binding mechanism within the malaria parasite which will help guide our synthesis of novel analogs for future drug discovery.