Esponjas

Pure Appl. Chem., Vol. 81, No. 6, pp. 1113–1121, 2009. DRAFT doi:10.1351/PAC-CON-08-10-07 © 2009 IUPAC

Chemical warfare in the sea: The search for antibiotics from Red Sea corals and sponges*
Dovi Kelman1,‡, Yoel Kashman1,2, Russell T. Hill5, Eugene Rosenberg3, and Yossi Loya1,4
Center for High Throughput Screening (HTS) of Novel Bioactive Compounds, 2School of Chemistry, 3Department ofMolecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, 4Department of Zoology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel; 5Center of Marine Biotechnology, University of Maryland Biotechnology Institute, 701 East Pratt Street, Baltimore, MD, USA Abstract: Marine sponges and corals are widely recognized as rich sources of novelbioactive 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 isolatedfrom 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 ofwhich 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 againstseawater 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 otherAlphaproteobacteria 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. Keywords: marine natural products; antimicrobial activity;sponges; corals; Red Sea; terpenes; alkaloids; halitoxins.
1National

*Paper based on a presentation at the International Conference on Biodiversity and Natural Products (ICOB-6 & ISCNP-26), 13–18 July 2008, Charlottetown, Prince Edward Island, Canada. Other presentations are published in this issue, pp. 1001–1129. ‡Corresponding author: E-mail: dovi.kelman@gmail.com

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D. KELMAN etal.

CORAL/SPONGE–MICROBE INTERACTIONS AND ANTIMICROBIAL DEFENSE Bacteria and other microorganisms are ubiquitous in the marine environment. They are taxonomically diverse, biologically active, and colonize all marine habitats, from the deep oceans to the shallowest estuaries [1], as well as coral reefs [2]. Living benthic marine organisms such as corals and sponges are frequently colonized bybacteria [2–4]. Moreover, the surface of living corals is covered by mucus [5]. This mucus layer is colonized by bacteria, allowing for the establishment of a bacterial community that can be characteristic of a particular coral species [3,4,6–8]. Some of these bacteria can be pathogenic and may initiate diseases such as black band disease [9], white plague type II [10,11], and tissue necrosis...