Abstract
With the global emergence of multiresistant bacteria there is an increasing demand for development of new treatments to combat pathogens. Bacterial cell–cell communication [quorum sensing (QS)] regulates expression of virulence factors in a number of bacterial pathogens and is a new promising target for the control of infectious bacteria. We present the results of screening of 284 extracts of marine organisms from the Great Barrier Reef, Australia, for their inhibition of QS. Of the 284 extracts, 64 (23%) were active in a general, LuxR-derived QS screen, and of these 36 (56%) were also active in a specific Pseudomonas aeruginosa QS screen. Extracts of the marine sponge Luffariella variabilis proved active in both systems. The secondary metabolites manoalide, manoalide monoacetate, and secomanoalide isolated from the sponge showed strong QS inhibition of a lasB::gfp(ASV) fusion, demonstrating the potential for further identification of specific QS antagonists from marine organisms.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andersen JB, Heydorn A, Hentzer M, Eberl L, Geisenberger O, Christensen BB, Molin S, Givskov M (2001) gfp based N-acyl-homoserine-lactone monitors for detection of bacterial communication. Appl Environ Microbiol 67, 575–585
Bertani G (1951) Studies on lysogenesis I The mode of phage liberation by lysogenic Escherichia coli. J Bacteriol 62, 293–300
Bianco ID, Kelley MJ, Crowl RM, Dennis EA (1995) Identification of two specific lysines responsible for the inhibition of phospholipase A2 by manoalide. Biochim Biophys Acta 1250, 197–203
Clark DJ, Maaloe O (1967) DNA replication and the division cycle in Escherichia coli. 23, 99–112
de Nys R, Givskov M, Kumar N, Kjelleberg S, Steinberg PD (2006) Furanones. Prog Mol Subcell Biol 42, 55–86
Erhardt H, Knop D (2005) Corals Indo-Pacific Field Guide (Frankfurt: IKAN Unterwasserarchiv)
Ettinger-Epstein P, Motti CA, de Nys R, Wright AD, Battershill CN, Tapiolas DM (2007) Acetylated sesterterpenes from the Great Barrier Reef sponge Luffariella variabilis. J Nat Prod 70, 648–651
Fabricius K, Aldersdale P (2001) Soft Corals and Sea Fans: A Comprehensive Guide to the Tropical Shallow Water Genera of the Central-West Pacific, the Indian Ocean and the Red Sea (Surrey Hills, Melbourne Australia: New Litho)
Fenical W, Jensen PR (2006) Developing a new resource for drug discovery: marine actinomycete bacteria. Nat Chem Biol 2, 666–673
Fuqua C, Winans SC, Greenberg EP (1994) Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol 176, 269–275
Gambello MJ, Kaye S, Iglewski BH (1993) LasR of Pseudomonas aeruginosa is a transcriptional activator of the alkaline protease gene (apr) and an enhancer of exotoxin A expression. Infect Immun 61, 1180–1184
Gao M, Teplitski M, Robinson JB, Bauer WD (2003) Production of substances by Medicago truncatula that affect bacterial quorum sensing. Mol Plant Microbe Interact 16, 827–834
Gay P, Le Coq D, Steinmetz M, Ferrari E, Hoch JA (1983) Cloning structural gene sacB, which codes for exoenzyme levansucrase of Bacillus subtilis: expression of the gene in Escherichia coli. J Bacteriol 153, 1424–1431
Givskov M, Molin S (1993) Secretion of Serratia liquefaciens phospholipase from Escherichia coli. Mol Microbiol 8, 229–242
Givskov M, Olsen L, Molin S (1988) Cloning and expression in Escherichia coli of the gene for extracellular phospholipase A1 from Serratia liquefaciens. J Bacteriol 170, 5855–5862
Givskov M, de Nys R, Manefield M, Gram L, Maximilien R, Eberl L, Molin S, Steinberg PD, Kjelleberg S (1996) Eukaryotic interference with homoserine lactone-mediated prokaryotic signalling. J Bacteriol 178, 6618–6622
Goslinger T, Behrens D, Williams G (1996) Coral Reef Animals of the Indo-Pacific (Petaluma, CA: Global InterPrint)
Harper MK, Bugni TS, Copp BR, et al. (2001) Mar Chem Ecol 3–69
Hentzer M, Givskov M (2003) Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. J Clin Invest 112, 1300–1307
Hentzer M, Riedel K, Rasmussen TB, et al. (2002) Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology 148, 87–102
Hentzer M, Wu H, Andersen JB, et al. (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22, 3803
Hooper JNA, Van Soest RW (2002) Systema Porifera A Guide to the Classification of Sponges, Vol. 1 and 2 (New York: Kluwer Academic/Plenum)
Huisman J (2000) Marine Plants of Australia. (Nedlands, Western Australia: University of Western Australia Press)
Manefield M, Harris L, Rice SA, de Nys R, Kjelleberg S (2000) Inhibition of luminescence and virulence in the black tiger prawn (Penaeus monodon) pathogen Vibrio harveyi by intercellular signal antagonists. Appl Environ Microbiol 66, 2079–2084
Marris E (2006) Marine natural products: drugs from the deep. Nature 443, 904–905
Miller JH (1972) Exp Mol Genet
Newman DJ, Cragg GM (2004a) Marine natural products and related compounds in clinical and advanced preclinical trials. J Nat Prod 67, 1216–1238
Newman DJ, Cragg GM (2004b) Advanced preclinical and clinical trials of natural products and related compounds from marine sources. Curr Med Chem 11, 1693–1713
Paterson I, Anderson EA (2005) The renaissance of natural products as drug candidates. Science 310, 451–453
Paul VJ, Puglisi MP, Ritson-Williams R (2006) Marine chemical ecology. Nat Prod Rep 23, 153–180
Potts BC, Faulkner DJ, Jacobs RS (1992) Phospholipase A2 inhibitors from marine organisms. 55, 1701–1717
Proksch P, Edrada RA, Ebel R (2002) Drugs from the seas—current status and microbiological implications. 59, 125–134
Rasch M, Buch C, Austin B, et al. (2004) An inhibitor of bacterial quorum sensing reduces mortalities caused by Vibriosis in rainbow trout (Oncorhynchus mykiss, Walbaum). Syst Appl Microbiol 27, 350–359
Rasmussen TB, Givskov M (2006) Quorum-sensing inhibitors as anti-pathogenic drugs. Int J Med Microbiol 296, 149–161
Rasmussen TB, Bjarnsholt T, Skindersoe ME, Hentzer M, Kristoffersen P, Kote M, Nielsen J, Eberl L, Givskov M (2005a) Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector. J Bacteriol 187, 1799–1814
Rasmussen TB, Skindersoe ME, Bjarnsholt T, et al. (2005b) Identity and effects of quorum-sensing inhibitors produced by Penicillium species. Microbiology 151, 1325–1340
Reacher MH, Shah A, Livermore DM, et al. (2000) Bacteraemia and antibiotic resistance of its pathogens reported in England and Wales between 1990 and 1998: trend analysis. Br Med J 320, 213–216
Slaughter JC (1999) The naturaly occuring furanones: formation and function from pheromone to food. Biol Rev Camb Philos Soc 74, 259–276
Tenover FC, Hughes JM (1996) The challenges of emerging infectious diseases. Development and spread of multiply-resistant bacterial pathogens. JAMA 275, 300–304
Toder DS, Gambello MJ, Iglewski BH (1991) Pseudomonas aeruginosa LasA: a second elastase under the transcriptional control of lasR. Mol Microbiol 5, 2003–2010
Tsuda M, Shigemori H, Ishibashi M, Saski T, Kobayashi J (2002) Luffariolides A-E, new cytotoxic sesterterpenes from the Okinawan marine sponge Luffariella sp. 3503–3507
Veron JEN (1993) Corals of Asia and the Indo-Pacific Angus and Robertson. North Ryde, Australia first published 1986
Acknowledgment
The field work was supported by grants from the Leo Pharma Research Foundation, the DTU Foundation for Polytechnic Teachers, and the Danish Research Council for Technique and Production to M.G.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Skindersoe, M.E., Ettinger-Epstein, P., Rasmussen, T.B. et al. Quorum Sensing Antagonism from Marine Organisms. Mar Biotechnol 10, 56–63 (2008). https://doi.org/10.1007/s10126-007-9036-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10126-007-9036-y