Overview

Greater than half of marketed drugs owe their origins to chemistry found in nature (1). Throughout the latter half of the 20th century, soil microbes were the primary source for new antibiotics, but it wasn’t long before continuous rediscovery of known compounds and lack of innovative search strategies hampered new compound discovery. As a result, natural products drug discovery research in recent decades has turned to the marine environment. This shift in focus has provided a wealth of new chemical compounds and in some cases, marketed drugs, often from sponges and their associated microbes (2-5).

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St. Lawrence River freshwater sponge.

Surprisingly, very little is known of the diversity and distribution of sponges and their associated microbial communities in freshwater ecosystems like the Great Lakes (6-8). Even less has been explored related to the therapeutic potential of compounds they produce (9-15). In the Murphy Lab, we have recently assembled a team of citizen scientist divers throughout the Great Lakes region to collect freshwater sponge samples. Together we are testing the hypothesis that freshwater sponges are an important resource for novel drug-leads.

The Murphy lab focuses on drug discovery from bacteria in the Great Lakes and is among the first to apply the marine drug discovery paradigm to freshwater environments, having already discovered a very potent and selective class of antibiotic drug-leads from Lake Michigan that inhibit drug-resistant TB (16). Our new freshwater sponge study engages citizen scientist divers in a collaboration to help in solving global health problems such as the fight against drug-resistant TB. Additionally, our collaborative study of freshwater sponge distribution and diversity across the Great Lakes will add to the understanding of the world’s largest freshwater resource, providing public education and significant leverage for freshwater ecosystem conservation.

Projected Outcomes: 

  1. Study of the diversity and distribution of sponges across the Great Lakes will provide leverage for freshwater ecosystem conservation and management.
  2. Citizen scientist divers will find added purpose in underwater exploration by improving upon knowledge of freshwater ecology while contributing to natural resource conservation and the fight against disease.
  3. Great Lakes biodiversity and drug discovery will be publicized through the creation of underwater videos and press releases, bringing attention to conservation and natural products research as our group has with past project features in ScienceDaily (17), The Toronto Star (18), NPR Radio (19), and C&E News (20).
  4. This study aims to contribute new lead molecules to combat drug-resistant infectious diseases, with a focus on M. tuberculosis.
  5. Collection efforts will generate several projects for undergraduate and graduate researchers in our laboratory. These results are regularly disseminated to the scientific community and beyond.

References:

  1. Newman, D. J.; Cragg, G. M. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J. Nat. Prod. 2012, 75, 311-335.
  2. Fenical, W.; Jensen, P. R. Developing a new resource for drug discovery: marine actinomycete bacteria. Nat. Chem. Biol. 2006, 2, 666-673.
  3. Huyck, T. K.; Gradishar, W.; Manuguid, F.; Kirkpatrick, P. Eribulin mesylate. Nat Rev Drug Discov 2011, 10, 173-174.
  4. Bewley, C. A.; Faulkner, D. J. Lithistid Sponges: Star Performers or Hosts to the Stars. Angewandte Chemie International Edition 1998, 37, 2162-2178.
  5. Pettit, G. R.; Herald, C. L.; Boyd, M. R.; Leet, J. E.; Dufresne, C.; Doubek, D. L.; Schmidt, J. M.; Cerny, R. L.; Hooper, J. N.; Rützler, K. C. Isolation and structure of the cell growth inhibitory constituents from the western Pacific marine sponge Axinella sp. J. Med. Chem. 1991, 34, 3339-3340.
  6. Lauer, T. E.; Spacie, A. New Records of Freshwater Sponges (Porifera) for Southern Lake Michigan. Journal of Great Lakes Research 1996, 22, 77-82.
  7. Lauer, T.E.; Barnes, D.K. Distribution of freshwater sponges and bryozoans in Northwest Indiana. Proc. Indiana Acad. Sci. 2003112, 29-3 5.
  8. Reiswig, H. M.; Frost, T. M.; Ricciardi, A. Ecology and classification of North American freshwater invertebrates. Third Ed. ed.; Thorp, J. H.; Alan, P. C., Eds. Academic Press: London, 2010; pp 91-124.
  9. Imbs, A. B.; Vereshchagin, A. L. Isolation and characteristic of super long-chain unsaturated aldehydes from the freshwater sponge Lubomirskia baicalensis. Russ. J. Bioorg. Chem. 2005, 31, 651-656.
  10. Imbs, A. B.; Rodkina, S. A. Trans and positional ethylenic bonds in two dominant isomers of eicosapentaenoic acid from the freshwater sponge Baicalospongia bacillifera. Lipids 2005, 40, 963-968.
  11. Řezanka, T.; Sigler, K.; Dembitsky, V. M. Syriacin, a novel unusual sulfated ceramide glycoside from the freshwater sponge Ephydatia syriaca (Porifera, Demospongiae, Spongillidae). Tetrahedron 2006, 62, 5937-5943.
  12. Hu, J.; Zhao, Y.; Chen, J.; Miao, Z.; Zhou, J. A new spongilipid from the freshwater sponge Spongilla lacustris. Bull. Korean Chem. Soc. 2009, 30, 1170-1172.
  13. Mazur, A. A new sponge sterol. J. Am. Chem. Soc. 1941, 63, 883-884.
  14. Makarieva, T. N.; Bondarenko, I. A.; Dmitrenok, A. S.; Boguslavsky, V. M.; Stonik, V. A.; Chernih, V. I.; Efremova, S. M. Natural Products from Lake Baikal Organisms, I. Baikalosterol, a Novel Steroid with an Unusual Side Chain, and Other Metabolites from the Sponge Baicalospongia bacilifera. Journal of Natural Products 1991, 54, 953-958.
  15. Keller-Costa, T.; Jousset, A.; van Overbeek, L.; van Elsas, J. D.; Costa, R. The freshwater sponge Ephydatia fluviatilis harbours diverse Pseudomonas species (Gammaproteobacteria, Pseudomonadales) with broad-spectrum antimicrobial activity. PLoS One 2014, 9, e88429.
  16. Mullowney, M. W.; Hwang, C. H.; Newsome, A. G.; Wei, X.; Tanouye, U.; Wan, B.; Carlson, S.; Barranis, N. J.; Krishnamoorthy, K.; White, J.; Blair, R.; Lee, H.; Rathod, P. K.; Parish, T.; Cho, S.; Franzblau, S. G.; Murphy, B. T. Diaza-anthracene antibiotics from a freshwater-derived actinomycete that selectively inhibit M. tuberculosis. ACS Infect. Dis. 2015, submitted 01/12/2015.
  17. Chicago, U. o. I. a. “Key to TB cure could lie underwater”. ScienceDaily 2013, www.sciencedaily.com/releases/2013/03/130307190524.htm (accessed January 31, 2015).
  18. Yang, J. “Antibiotic Hunters”. The Toronto Star 2014, http://thestar.com/antibiotics (accessed January 31, 2015).
  19. Williams, R. “Researcher hunts for new medicines in the Great Lakes.”. NPR Radio: “The Environmental Report.” 2014, http://michiganradio.org/post/researcher-hunts-new-medicines-great-lakes (accessed January 31, 2015).
  20. Yarnell, A. “Bringing Blue To A Plate Near You”. Chemical & Engineering News 2012, http://cen.acs.org/articles/90/i37/Bringing-Blue-Plate-Near.html (accessed January 31, 2015).

 

 

 

Underwater photograph of sponges on Dump Barge, OH. credit: David VanZandt, CLUE

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