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Pure Appl. Chem., 2009, Vol. 81, No. 6, pp. 1113-1121

Published online 2009-05-05

Chemical warfare in the sea: The search for antibiotics from Red Sea corals and sponges

Dovi Kelman1*, Yoel Kashman1,2, Russell T. Hill3, Eugene Rosenberg4 and Yossi Loya5,1

1 National Center for High Throughput Screening (HTS) of Novel Bioactive Compounds, Tel Aviv University, Tel Aviv, Israel
2 School of Chemistry, Tel Aviv University, Tel Aviv, Israel
3 Center of Marine Biotechnology, University of Maryland Biotechnology Institute, 701 East Pratt Street, Baltimore, MD 21202, USA
4 Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
5 Department of Zoology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

Abstract: Marine sponges and corals are widely recognized as rich sources of novel bioactive natural products. These organisms are frequently colonized by bacteria. Some of these bacteria can be pathogenic or serve as beneficial symbionts. Therefore, these organisms need to regulate the bacteria they encounter and resist microbial pathogens. One method is by chemical defense. Antimicrobial assays performed with extracts of 23 Red Sea corals and sponges against bacteria isolated from their natural environment revealed considerable variability in antimicrobial activity. Soft corals exhibited appreciable activity; sponges showed variability, and stony corals had little or no activity. Among the soft corals, Xenia macrospiculata exhibited the highest activity. Bioassay-directed fractionation of the extract indicated that the activity was due to a range of compounds, one of which was isolated and identified as the diterpene desoxyhavannahine. Among the sponges, Amphimedon chloros exhibited strong activity. Bioassay-directed fractionation resulted in the isolation of the pyridinium alkaloid antibiotics, the halitoxins and amphitoxins. These compounds showed selective activity against specific bacteria, rather than being broad-spectrum. They were highly active against seawater bacteria, whereas bacteria associated with the sponge were resistant. This selective toxicity may be important in enabling certain bacteria to live in close association with their sponge host while it maintains a chemical defense against microbial pathogenesis. The halitoxin-resistant bacteria were identified by 16S rRNA gene analysis as Alphaproteobacteria, closely related to other Alphaproteobacteria isolated from various marine sponges. The study of microbial communities associated with sponges and corals has important implications for the production of symbiont-derived bioactive compounds and for the use of corals and sponges as source material for microbial diversity in screening programs for natural products.