Planta Med 2014; 80(14): 1234-1246
DOI: 10.1055/s-0034-1383001
Reviews
Georg Thieme Verlag KG Stuttgart · New York

Exploring Marine Resources for Bioactive Compounds

Paula Kiuru
1   Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Finland
,
M. Valeria DʼAuria
2   Department of Pharmacy, University of Naples Federico II, Naples, Italy
,
Christian D. Muller
3   Laboratoire dʼInnovation Thérapeutique UMR CNRS 7200, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France
,
Päivi Tammela
4   Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, Finland
,
Heikki Vuorela
5   Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Finland
,
Jari Yli-Kauhaluoma
1   Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Finland
› Author Affiliations
Further Information

Publication History

received 09 April 2014
revised 09 July 2014

accepted 09 July 2014

Publication Date:
09 September 2014 (online)

Abstract

Biodiversity in the seas is only partly explored, although marine organisms are excellent sources for many industrial products. Through close co-operation between industrial and academic partners, it is possible to successfully collect, isolate and classify marine organisms, such as bacteria, fungi, micro- and macroalgae, cyanobacteria, and marine invertebrates from the oceans and seas globally. Extracts and purified compounds of these organisms can be studied for several therapeutically and industrially significant biological activities, including anticancer, anti-inflammatory, antiviral, antibacterial, and anticoagulant activities by applying a wide variety of screening tools, as well as for ion channel/receptor modulation and plant growth regulation. Chromatographic isolation of bioactive compounds will be followed by structural determination. Sustainable cultivation methods for promising organisms and biotechnological processes for selected compounds can be developed, as well as biosensors for monitoring the target compounds. The (semi)synthetic modification of marine-based bioactive compounds produces their new derivatives, structural analogs and mimetics that could serve as hit or lead compounds and be used to expand compound libraries based on marine natural products. The research innovations can be targeted for industrial product development in order to improve the growth and productivity of marine biotechnology. Marine research aims at a better understanding of environmentally conscious sourcing of marine biotechnology products and increased public awareness of marine biodiversity. Marine research is expected to offer novel marine-based lead compounds for industries and strengthen their product portfolios related to pharmaceutical, nutraceutical, cosmetic, agrochemical, food processing, material and biosensor applications.

 
  • References

  • 1 Blunt JW, Munro MHG. Dictionary of marine natural products. Boca Raton: Chapmann & Hall/CRC; 2007. (Available at http://dmnp.chemnetbase.com/intro/index.jsp. Accessed July 2, 2014.)
  • 2 Mora C, Tittensor DP, Adl S, Simpson AGB, Worm B. How many species are there on Earth and in the ocean?. PLoS Biol 2011; 9: e1001127
  • 3 Sennet SH. Marine chemical ecology: applications in marine biomedical prospecting. In: McClintock JB, Baker BJ, editors Marine chemical ecology. Boca Raton: CRC Press; 2001: 523-542
  • 4 Blunt JW, Copp BR, Keyzers RA, Munro MHG, Prinsep MR. Marine natural products. Nat Prod Rep 2014; 31: 160-258
  • 5 Blunt JW, Copp BR, Keyzers RA, Munro MHG, Prinsep MR. Marine natural products. Nat Prod Rep 2013; 30: 237-323
  • 6 Cragg GM, Newman DJ. Natural products: a continuing source of novel drug leads. Biochim Biophys Acta 2013; 1830: 3670-3695
  • 7 Mayer AM, Glaser KB, Cuevas C, Jacobs RS, Kem W, Little RD, McIntosh JM, Newman DJ, Potts BC, Shuster DE. The odyssey of marine pharmaceuticals: a current pipeline perspective. Trends Pharmacol Sci 2010; 31: 255-265
  • 8 Cuevas C, Pérez M, Martín MJ, Chicharro JL, Fernández-Rivas C, Flores M, Francesch A, Gallego P, Zarzuelo M, de La Calle F, García J, Polanco C, Rodríguez I, Manzanares I. Synthesis of ecteinascidin ET–743 and phthalascidin Pt–650 from cyanosafracin B. Org Lett 2000; 2: 2545-2548
  • 9 Kem W, Soti F, Wildeboer K, LeFrancois S, MacDougall K, Wei DQ, Chou KC, Arias HR. The nemertine toxin anabaseine and its derivative DMXBA (GTS–21): chemical and pharmacological properties. Mar Drugs 2006; 4: 255-273
  • 10 Molinski TF, Dalisay DS, Lievens SL, Saludes JP. Drug development from marine natural products. Nat Rev Drug Discov 2009; 8: 69-85
  • 11 Coll M, Carreras M, Ciercoles C, Cornax MJ, Gorelli G, Morote E, Saez R. Assessing fishing and marine biodiversity changes using fishersʼ perceptions: the Spanish Mediterranean and Gulf of Cadiz case study. PLoS One 2014; 9: e85670/1-e85670/15
  • 12 Cragg GM, Katz F, Newman DJ, Rosenthal J. Legal and ethical issues involving marine biodiscovery and development. In: Fattorusso E, Gerwick WH, Taglialatela-Scafati O, editors Handbook of marine natural products. Dordrecht: Springer; 2012: 1314-1342
  • 13 Gareth RJ, Jennifer MG. The experience and evolution of trust: implications for cooperation and teamwork. Acad Manage Rev 1998; 23: 531-546
  • 14 Kornprobst JM. Encyclopedia of marine natural products, Volume 1. Weinheim: Wiley-Blackwell; 2010: 43-169 447
  • 15 Rothschild LJ, Mancinelli RL. Life in extreme environments. Nature 2001; 409: 1092-1101
  • 16 Thomas TRA, Kavlekar DP, LokaBharathi PA. Marine drugs from sponge-microbe association–A review. Mar Drugs 2010; 8: 1417-1468
  • 17 Felczykowska A, Bloch SK, Nejman-Faleńczyk B, Barańska S. Metagenomic approach in the investigation of new bioactive compounds in the marine environment. Acta Biochim Pol 2012; 59: 501-505
  • 18 Butler MS, Blaskovich MA, Cooper MA. Antibiotics in the clinical pipeline in 2013. J Antibiot 2013; 66: 571-591
  • 19 Jang KH, Nam SJ, Locke JB, Kauffman CA, Beatty DS, Paul LA, Fenical W. Anthracimycin, a potent anthrax antibiotic from a marine-derived actinomycete. Angew Chem Int Ed 2013; 52: 7822-7824
  • 20 Mahajan G, Thomas B, Parab R, Patel ZE, Kuldharan S, Yemparala V, Mishra PD, Ranadive P, DʼSouza L, Pari K, Girish HS. In vitro and in vivo activities of antibiotic PM181104. Antimicrob Agents Chemother 2013; 57: 5315-5319
  • 21 Singh S, Kate BN, Banerjee UC. Bioactive compounds from cyanobacteria and microalgae: an overview. Crit Rev Biotechnol 2005; 25: 73-95
  • 22 Burja AM, Banaigs B, Abou-Mansourc E, Burgess JG, Wright PC. Marine cyanobacteria–a prolific source of natural products. Tetrahedron 2001; 57: 9347-9377
  • 23 Welker M, von Döhren H. Cyanobacterial peptides – natureʼs own combinatorial biosynthesis. FEMS Microbiol Rev 2006; 30: 530-563
  • 24 Cohen Z, Margheri MC, Tomaselli L. Chemotaxonomy of cyanobacteria. Phytochemistry 1995; 40: 1155-1158
  • 25 Welker M, Brunke M, Preussel K, Lippert I, von Döhren H. Diversity and distribution of Microcystis (Cyanobacteria) oligopeptide chemotypes from natural communities studied by single–colony mass spectrometry. Microbiology 2004; 150: 1785-1796
  • 26 Welker M, Christiansen G, von Döhren H. Diversity of coexisting Planktothrix (Cyanobacteria) chemotypes deduced by mass spectral analysis of microystins and other oligopeptides. Arch Microbiol 2004; 182: 288-298
  • 27 Diehnelt CW, Dugan NR, Peterman SM, Budde WL. Identification of microcystin toxins from a strain of Microcystis aeruginosa by liquid chromatography introduction into a hybrid linear ion trap – Fourier transform ion cyclotron resonance mass spectrometer. Anal Chem 2006; 78: 501-512
  • 28 Walker M, Erhard M. Consistency between chemotyping of single filaments of Planktothrix rubescens (Cyanobacteria) by MALDI–TOF and the peptide patterns of strains determined by HPLC–MS. J Mass Spectrom 2007; 42: 1062-1068
  • 29 Shimizu Y. Microalgal metabolites. Chem Rev 1993; 93: 1685-1698
  • 30 Daranas AH, Norte M, Fernández JJ. Toxic marine microalgae. Toxicon 2001; 39: 1101-1132
  • 31 Nicolaou KC, Aversa RJ. Maitotoxin: an inspiration for synthesis. Isr J Chem 2011; 51: 359-377
  • 32 Matsubara K. Recent advances in marine algal anticoagulants. Curr Med Chem Cardiovasc Hematol Agents 2004; 2: 13-19
  • 33 Ekanayake PM, Nikapitiya C, De Zoysa M, Whang I, Kim SJ, Lee J. Novel anticoagulant compound from fermented red alga Pachymeniopsis elliptica . Eur Food Res Technol 2008; 227: 897-903
  • 34 Pushpamali WA, Nikapitiya C, De Zoysa M, Whang I, Kim SJ, Lee J. Isolation and purification of an anticoagulant from fermented red seaweed Lomentaria catenata . Carbohydr Polym 2008; 73: 274-279
  • 35 de Nys R, Steinberg PD. Linking marine biology and biotechnology. Curr Opin Biotechnol 2002; 13: 244-248
  • 36 Duarte K, Rocha-Santos TAP, Freitas AC, Duarte AC. Analytical techniques for discovery of bioactive compounds from marine fungi. Trends Anal Chem 2012; 34: 97-110
  • 37 Bergmann W, Feeney RJ. Contributions to the study of marine products. XXXII. The nucleosides of sponges I. J Org Chem 1951; 16: 981-987
  • 38 Lemaire P. Evolutionary crossroads in developmental biology: the tunicates. Development 2011; 138: 2143-2152
  • 39 Lewis RJ, Garcia ML. Therapeutic potential of venom peptides. Nat Rev Drug Discov 2003; 2: 790-802
  • 40 Clark RJ, Jensen J, Nevin ST, Callaghan BP, Adams DJ, Craik DJ. The engineering of an orally active conotoxin for the treatment of neuropathic pain. Angew Chem Int Ed 2010; 49: 6545-6548
  • 41 Rocha J, Peixe L, Gomes NCM, Calado R. Cnidarians as a source of new marine bioactive compounds–an overview of the last decade and future steps for bioprospecting. Mar Drugs 2011; 9: 1860-1886
  • 42 Mackie GO. Whatʼs new in cnidarian biology?. Can J Zool 2002; 80: 1649-1653
  • 43 Nelson JS. Fishes of the world, 4th edition. Hoboken: John Wiley & Sons Inc; 2006: 2-5
  • 44 Reddy LH, Couvreur P. Squalene: a natural triterpene for use in disease management and therapy. Adv Drug Deliv Rev 2009; 61: 1412-1426
  • 45 Nieto FR, Cobos EJ, Tejada MÁ, Sánchez-Fernández C, González-Cano R, Cendán CR. Tetrodotoxin (TTX) as a therapeutic agent for pain. Mar Drugs 2012; 10: 281-305
  • 46 Esteves-Ferreira AA, Correa DM, Carneiro APS, Rosa RM, Loterio R, Araujo WL. Comparative evaluation of different preservation methods for cyanobacterial strains. J Appl Phycol 2013; 25: 919-929
  • 47 Guillard RRL. Purification methods for microalgae. In: Andersen AR, editor Algal culturing techniques. China: Elsevier Academic Press; 2005: 117-132
  • 48 Bohlin L, Alsmark C, Goeransson U, Klum M, Weden C, Backlund A. In: Tringali C, editor. Bioactive compounds from natural sources. 2nd. edition. Boca Raton: CRC Press; 2012: 1-36
  • 49 Eriksen NT. The technology of microalgal culturing. Biotechnol Lett 2008; 30: 1525-1536
  • 50 Schmidt RS. Heterotrophic high cell–density fed–batch cultures of the phycocyanin–producing red alga Galdieria sulphuraria . Biotechnol Bioengin 2005; 90: 77-84
  • 51 Kupchan SM, Britton RW, Ziegler MF, Sigel CW. Bruceantin, a new potent antileukemic simaroubolide from Brucea antidysenterica . J Org Chem 1973; 38: 178-179
  • 52 Donia MS, Ruffner DE, Cao S, Schmidt EW. Accessing the hidden majority of marine natural products through metagenomics. Chembiochem 2011; 12: 1230-1236
  • 53 Breton RC, Reynolds WF. Using NMR to identify and characterize natural products. Nat Prod Rep 2013; 30: 501-524
  • 54 Ghitti M, Musco G, Spitaleri A. NMR and computational methods in the structural and dynamic characterization of ligand-receptor interactions. Adv Exp Med Biol 2014; 805: 271-304
  • 55 Matsumori N, Kaneno D, Murata M, Nakamura H, Tachibana K. Stereochemical determination of acyclic structures based on carbon-proton spin-coupling constants. A method of configuration analysis for natural products. J Org Chem 1999; 64: 866-876
  • 56 Seco JM, Quiñoá E, Riguera R. The assignment of absolute configuration by NMR. Chem Rev 2004; 104: 17-117
  • 57 Lee JA, Berg EL. Neoclassic drug discovery: the case for lead generation using phenotypic and functional approaches. J Biomol Screen 2013; 18: 1143-1155
  • 58 Fishburn CS. Translational research: the changing landscape of drug discovery. Drug Discov Today 2013; 18: 487-494
  • 59 Lang PK, Yeow K, Nichols A, Sheer A. Cellular imaging in drug discovery. Nat Rev Drug Discov 2006; 5: 343-356
  • 60 Lee JA, Uhlik MT, Moxham CM, Tomandl D, Sall DJ. Modern phenotypic drug discovery is a viable, neoclassic pharma strategy. J Med Chem 2012; 55: 4527-4538
  • 61 Sams-Dodd F. Is poor research the cause of the declining productivity of the pharmaceutical industry? An industry in need of a paradigm shift. Drug Discov Today 2013; 18: 211-217
  • 62 Harvey AL. Natural products as a screening resource. Curr Opin Chem Biol 2007; 11: 480-484
  • 63 Bugni TS, Richards B, Bhoite L, Cimbora D, Harper MK, Ireland CM. Marine natural product libraries for high–throughput screening and rapid drug discovery. J Nat Prod 2008; 71: 1095-1098
  • 64 Tawfike AF, Viegelmann C, Edrada-Ebel R. Metabolomics and dereplication strategies in natural products. Methods Mol Biol 2013; 1055: 227-244
  • 65 Larsen TO, Smedsgaard J, Nielsen KF, Hansen ME, Frisvad JC. Phenotypic taxonomy and metabolite profiling in microbial drug discovery. Nat Prod Rep 2005; 22: 672-695
  • 66 Koehn FE, Carter GT. The evolving role of natural products in drug discovery. Nat Rev Drug Discov 2005; 4: 206-220
  • 67 Florence GJ, Gardner NM, Ian Paterson I. Development of practical syntheses of the marine anticancer agents discodermolide and dictyostatin. Nat Prod Rep 2008; 25: 342-375
  • 68 Chen JC, Chen XC, Willot M, Zhu J. Asymmetric total syntheses of ecteinascidin 597 and ecteinascidin 583. Angew Chem Int Ed 2006; 45: 8028-8032
  • 69 Shang S, Tan DS. Advancing chemistry and biology through diversity–oriented synthesis of natural product–like libraries. Curr Opin Chem Biol 2005; 9: 248-258
  • 70 Mantovani A, Balkwill F. RalB signaling: a bridge between inflammation and cancer. Cell 2006; 127: 42-44
  • 71 Castellani P, Balza E, Rubartelli A. Inflammation, DAMPs, tumor development, and progression: a vicious circle orchestrated by redox signaling. Antioxid Redox Sign 2014; 20: 1086-1097
  • 72 Luo JL, Kamata H, Karin M. IKK/NF-κB signaling: balancing life and death – a new approach to cancer therapy. J Clin Invest 2005; 115: 2625-2632
  • 73 Luo JL, Maeda S, Hsu LC, Yagita H, Karin M. Inhibition of NF-κB in cancer cells converts inflammation- induced tumor growth mediated by TNFα to TRAIL-mediated tumor regression. Cancer Cell 2004; 3: 297-305
  • 74 Karin M, Greten FR. NF-κB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 2005; 10: 749-759
  • 75 Grienke U, Silke J, Tasdemir D. Bioactive compounds from marine mussels and their effects on human health. Food Chemistry 2014; 142: 48-60
  • 76 Kim JA, Kim SK. Bioactive peptides from marine sources as potential anti-inflammatory therapeutics. Curr Protein Pept Sci 2013; 14: 177-182
  • 77 Moczydlowski EG. The molecular mystique of tetrodotoxin. Toxicon 2013; 63: 165-183
  • 78 Greenberg EN. Ziconitide. J Pain Palliat Care Pharmacother 2011; 25: 380-381
  • 79 Adams DJ, Berecki G. Mechanisms of conotoxin inhibition of N-type (Cav2.2) calcium channels. Biochim Biophys Acta 2013; 1828: 1619-1628
  • 80 Kresse H, Belsey MJ, Rovin H. The antibacterial drugs market. Nat Rev Drug Discov 2007; 6: 19-20
  • 81 Weaver SC, Barrett A. Transmission cycles, host range, evolution and emergence of arboviral disease. Nat Rev Microbiol 2004; 2: 789-801
  • 82 Pialoux G, Gaüzère BA, Jauréguiberry S, Strobel M. Chikungunya, an epidemic arbovirosis. Lancet Infect Dis 2007; 7: 319-327
  • 83 Rezza G, Nicoletti L, Angelini R, Romi R, Finarelli AC, Panning M, Cordioli P, Fortuna C, Boros S, Magurano F, Silvi G, Angelini P, Dottori M, Ciufolini MG, Majori GC, Cassone A. Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet 2007; 370: 1840-1846
  • 84 Brummer-Korvenkontio M, Vapalahti O, Kuusisto P, Saikku P, Manni T, Koskela P, Nygren T, Brummer-Korvenkontio H, Vaheri A. Epidemiology of Sindbis virus infections in Finland 1981–96: possible factors explaining a peculiar disease pattern. Epidemiol Infect 2002; 129: 335-345
  • 85 Mayer AMS, Jacobson PB, Fenical W, Jacobs RS, Glaser KB. Pharmacological characterization of the pseudopterosins: novel anti-inflammatory natural products isolated from the Caribbean soft coral, Pseudopterogorgia elisabethae . Life Sci 1998; 62: PL401-PL407
  • 86 Castanaro J, Lasker HR. Effects of clipping on growth of colonies of the Caribbean gorgonian Pseudopterogorgia elisabethae . Invertebr Biol 2003; 122: 299-307
  • 87 Moore A. Blooming prospects? Humans have eaten seaweed for millennia; now microalgae are to be served up in a variety of novel health supplements, medicaments and preparations. EMBO Rep 2001; 2: 462-464
  • 88 Zhu D, Niu J, Shen S, Wang G. An economic assessment of astaxanthin production by large scale cultivation of Haematococcus pluvialis . Biotechn Adv 2011; 29: 568-574
  • 89 Picot C, Nguyen TA, Roudot AC, Parent-Massin DA. Preliminary risk assessment of human exposure to phycotoxins in shellfish: a review. Hum Ecol Risk Assess 2011; 17: 328-366
  • 90 Vilarino N, Louzao MC, Fraga M, Rodriguez LP, Botana LM. Innovative detection methods for aquatic algal toxins and their presence in the food chain. Anal Bioanal Chem 2013; 405: 7719-7732
  • 91 Campbell K. Biosensor technology for marine toxin analysis. In: Botana LM, editor Seafood and freshwater toxins, pharmacology, physiology, and detection. 3rd edition. Boca Raton: CRC Press; 2014: 347-366
  • 92 Eggins BR. Chemical sensors and biosensors. New York: John Wiley & Sons Inc; 2002: 5-9
  • 93 Huang PJJ, Khimji I, Liu J. Immobilization of fluorescent aptamer biosensors on magnetic microparticles and its potential application for ocean sensing. In: Tiquia-Arashiro SM, editor Molecular biological technologies for ocean sensing. Dearborn: Humana Press; 2012: 151-168
  • 94 Weigl BH, Bardell RL, Cabrera CR. Lab-on-a-chip for drug development. Adv Drug Deliv Rev 2003; 55: 349-377
  • 95 Erickson D, Li D. Integrated microfluidic devices. Anal Chim Acta 2004; 507: 11-26
  • 96 Marquette CA, Coulet PR, Blum LJ. Semi-automated membrane based chemiluminescent immunosensor for flow injection analysis of okadaic acid in mussels. Anal Chim Acta 1999; 398: 173-182
  • 97 Desmet C, Blum LJ, Marquette CA. Multiplex microarray ELISA versus classical ELISA, a comparison study of pollutant sensing for environmental analysis. Environ Sci Process Impacts 2013; 15: 1876-1882
  • 98 Yakes BJ, Prezioso SM, DeGrasse SL. Developing improved immunoassays for paralytic shellfish toxins: the need for multiple, superior antibodies. Talanta 2012; 99: 668-676
  • 99 Kulagina NV, Twiner MJ, Hess P, McMahon T, Satake M, Yasumoto T, Ramsdell JS, Doucette GJ, Ma W, OʼShaughnessy TJ. Detection of marine toxins, brevetoxin-3 and saxitoxin, in seawater using neuronal networks. Environ Sci Technol 2006; 40: 578-583
  • 100 Strik WA, Ördög V, Van Staden J, Jäger K. Cytokinin- and auxin-like activity in Cyanophyta and microalgae. J Appl Phycol 2002; 14: 215-221
  • 101 Karthikeyan N, Prasanna R, Nain L, Kaushik BD. Evaluating the potential of plant growth promoting cyanobacteria as inoculants for wheat. Eur J Soil Biol 2007; 43: 23-30
  • 102 Peuthert A, Chakrabarti S, Pflugmache S. Uptake of microcystins-LR and -LF (cyanobacterial toxins) in seedlings of several important agricultural plant species and the correlation with cellular damage (lipid peroxidation). Environ Toxicol 2007; 22: 436-442
  • 103 Zaccaro MC, Kato A, Zulpa G, Storni MM, Steyerthal N, Lobasso K, Stella AM. Bioactivity of Scytonema hofmanni (Cyanobacteria) in Lilium alexandrae in vitro propagation. Electr J Biotechnol 2006; 9: 210-214
  • 104 Berry JP, Gantar M, Perez MH, Berry G, Noriega FG. Cyanobacterial toxins as allelochemicals with potential applications as algaecides, herbicides and insecticides. Mar Drugs 2008; 6: 117-146
  • 105 Hellio C, Tsoukatou M, Maréchal JP, Aldred N, Beaupoil C, Clare AS, Vagias C, Roussis V. Inhibitory effects of Mediterranean sponge extracts and metabolites on larval settlement of the barnacle Balanus amphitrite . Mar Biotechnol 2005; 7: 297-305
  • 106 Chelossi E, Mancini I, Sepčić K, Turk T, Faimali M. Comparative antibacterial activity of polymeric 3-alkylpyridinium salts isolated from the Mediterranean sponge Reniera sarai and their synthetic analogues. Biomol Engin 2006; 23: 317-323
  • 107 Sjoegren M, Johnson AL, Hedner E, Dahlstroem M, Goeransson U, Shirani H, Bergman J, Jonsson PR, Bohlin L. Antifouling activity of synthesized peptide analogs of the sponge metabolite barettin. Peptides 2006; 27: 2058-2064
  • 108 Sjoegren M, Dahlstroem M, Goeransson U, Jonsson P, Bohlin L. Recruitment in the field of Balanus improvisus and Mytilus edulis in response to the antifouling cyclopeptides barettin and 8,9-dihydrobarettin from the marine sponge Geodia barrette . Biofouling 2004; 20: 291-297
  • 109 Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nature Rev Microbiol 2004; 2: 95-108
  • 110 Lear G, Lewis GD. Microbial biofilms: current research and applications. Norfolk: Caister Academic Press; 2012: 1-228
  • 111 Matz C, Webb JS, Schupp PJ, Phang SY, Penesyan A, Egan S, Steinberg P, Kjelleberg S. Marine biofilm bacteria evade eukaryotic predation by targeted chemical defense. PLoS One 2008; 3: 1-7
  • 112 Matz C. Struggle, communication, cooperation. Biochemical interactions in marine biofilms. Chem Unserer Zeit 2009; 43: 160-167
  • 113 Skogman M, Vuorela P, Fallarero A. Combining biofilm matrix measurements with biomass and viability assays in susceptibility assessments of antimicrobials against Staphylococcus aureus biofilms. J Antibiot 2012; 65: 453-459
  • 114 Manner S, Skogman M, Goeres D, Vuorela P, Fallarero A. Systematic exploration of natural and synthetic flavonoids for inhibition of Staphylococcus aureus biofilms. Int J Mol Sci 2013; 14: 19434-19451
  • 115 Ausbacher D, Fallarero A, Määttänen A, Kujala J, Ström MB, Vuorela PM. Staphylococcus aureus biofilm susceptibility to small and potent β2,2-amino acid derivatives. Biofouling 2014; 30: 81-93