Potential Therapeutics Isolated from Salinispora
Introduction
Rather than designing synthetic drugs, some researchers are exploring natural sources for cancer treatments and as models for future synthetic treatments. One promising source includes the recently discovered Salinispora bacteria, belonging to the order Actinomycetales (also known as actinomycetes). This order includes many species that have contributed to today’s naturally occurring antibiotics. It was originally believed that the gram positive Actinomycetales only existed in soil habitats, and that any actinomycetes found in marine environments came from spores produced by terrestrial species (1). However, in search of new actinomycetes as possible dug sources, Jensen and Fenical of the Scripps Institution of Oceanography in the late 1980s discovered actinomycetes (originally called MAR1) that required seawater for growth (2). In 2002, the separate strains of marine origin were found in tropical and subtropical sediment, and classified under the genus Salinispora, belonging to the family Micromonosporaceae. Two species have been formally identified as Salinispora arenicola and Salinispora tropica, while a third species of Salinispora pacifica is being studied (2,3). The Salinispora bacteria have, like the rest of their order, a variety of secondary metabolites that may be useful in the pharmeceutical industry, including the proteasome inhibitor salinosporamide A, which has entered the first phase of clinical trials as a cancer treatment (4). While the functions of some of the Salinispora metabolites are still unknown, these bacteria may offer researchers a source of new antibiotics and anticancer therapeutics.
Salinispora
Salinispora are aerobic, Gram-positive, non-acid fast bacteria (5). This species is found in marine sediment both near the shoreline, as well as at a depth of 2000 meters. It is has also been cultured in association with sea grass and algae (1, 2, 6). It is believed that like the related terrestrial actinomycetes, Salinispora are involved in decomposing organic materials along the ocean floor (6). Salinispora form branched, non-fragmenting hyphae that are 0.25 to .5 um in diameter, with N-glycolated muramic acid and meso-diaminopimelic acid in their cell wall peptidoglycan (5). These hyphae have been seen growing away from the pieces of shells or sand grains to which the bacteria appear attached (6). Major sugars used within these bacteria are galactose, arabinose, and xylose. Salinispora do not have mycolic acids, but contain anteiso-, saturated, and iso-fatty acids (5). Salt water or a salt-supplemented growth medium is required for growth, a key distinction between Salinispora and its close relatives. Salinispora growth occurs at a pH of 7-12 and 10-30°C. Salinispora form spores, 0.8 to 3.8 um in diameter, on short, spore bearing stalks known as sporophores,. These spores are smooth, non-motile, and can be produced in clusters or individually (5). Spores appear as darkened areas of cultured colonies. When cultured on nutrient rich media, the bacteria form orange and/or black colored colonies without the presence of aerial hyphae. On nutrient poor media, Salinispora form mycelia and produce diffusible orange, pink, dark brown, or black pigments (5).
Salinispora is currently divided into three species as determined by 16S rRNA gene sequence analysis. No overlap in secondary metabolic products between any of the defined species has been recorded (7). S. arenicola was found from coarse sand in marine sediments in Guam, the Red Sea, the Bahamas, Palau, the Sea of Cortez, and the U.S. Virgin Islands (8). Though several strains of this species have been acquired in various marine locations, the species-specific secondary metabolites have remained constant, suggesting they may be important for survival and can be used as a phenotypic indicator (7). The S. arenicola genome has been sequenced, and contains 5,786,361 bp (9). Its optimum growth occurs at 20-28°C with 25-50% seawater. Energy for this species is obtained through L-proline, L-threonine, L-tyrosine, arbutin, and (+)-D-salicin (5). S. tropica has only been cultured from marine sediment collection sites in the Bahamas (8). It grows optimally at 15-28°C, and obtains energy from inulin and galactose. S. pacifica has been cultured from Palau, the Red Sea, and Guam, and is still being categorized. Though these bacteria are mostly obtained from marine sediment, S. arenicola and S. pacifica have been located in a sponge from the Great Barrier Reef, and S. pacifica has been identified with an ascidian in Fiji (7).
This genus of marine bacteria produces an array of secondary metabolites. These include, anticancer, antibiotic, antiviral, and anti-inflammatory agents. Not all of the metabolites produced by the Salinispora species have a known biological activity, and of those that have demonstrated a useful biological effect not all have known molecular targets (8).
Anticancer agents
Include some current research in each topic, with at least one figure showing data.
Antibiotics Anti-inflammatory Compounds
Include some current research in each topic, with at least one figure showing data.
Conclusion
Overall paper length should be 3,000 words, with at least 3 figures.
References
1. Mincer, T.J., P.R. Jensen, C.A. Kauffman, and W. Fenical. 2002. Widespread and Persistent Populations of a Major New Marine Actinomycete Taxon in Ocean Sediments. Applied and Experimental Microbiology. 68: 5005-5011.
2. Fenical, W., P.R. Jensen, M.A. Palladino, K.S. Lam, G.K. Lloyd, and B.C. Potts. 2009. Discovery and development of the anticancer agent salinosporamide A (NPI-0052). Bioorganic & Medicinal Chemistry. 17: 2175-2180.
3. Udwary, D.W., L. Zeigler, R.N. Asolkar, V. Singan, A. Lapidus, W. Fenical, P.R. Jensen, and B.S. Moore. 2007. Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica. PNAS. 104 (25): 10376-10381.
4. Jensen, P.R., P.G. Williams, D.C. Oh, L. Zeigler, and W. Fenical. Species-Specific Secondary Metabolite Production in Marine Actinomycetes of the Genus Salinispora. 2006. Applied and Experimental Microbiology. 73(4): 1146-1152.
5. Maldonado, L.A., W. Fenical, P.R. Jensen, C.A. Kauffman, T.J. Mincer, A.C. Ward, A.T. Bull, and M. Goodfellow. 2005. Salinispora arenicola gen. nov., sp. nov. and Salinispora tropica sp. Nov., obligate marine actinomycetes belonging to the family Micromonosporaceae. International Journal of Systematic and Evolutionary Microbiology. 55: 1759-1766.
6. Jensen, P.R., P.G. Williams, D.C. Oh, L. Zeigler, and W. Fenical. 2007. Species-specific secondary metabolite production in marine Actinomycetes of the genus Salinispora. Applied and Experimental Microbiology. 73(4): 1146-1152.
Edited by a student of Joan Slonczewski for BIOL 238 Microbiology, 2009, Kenyon College.
