The objective of this study was to screen extracts of twenty Eastern European medicinal plants, using wild-type and reporter Chromobacterium violaceum bioassays, for novel components that target bacterial cells and their quorum sensing (QS) communication systems. Three types of activity and their combinations were revealed: (i) direct antimicrobial growth-inhibitory activity, (ii) non-specific and specific pro-QS activities, (iii) anti-QS activity. Among seven plant extracts showing direct growth-inhibitory activity, the strongest effect was shown by Arctostaphylos uva- -ursi (bearberry) leaves. Many plants stimulated violacein production by wild-type C. violaceum ATCC 31532 in a non-specific manner, and only the herb Bidens tripartita (three-lobe beggarticks) contained compounds that mimic acyl-homoserine lactone and operated as a QS agonist. Anti-QS activity was found in eleven plants including Quercus robur (oak) cortex, Betula verrucosa (birch) buds and Eucalyptus viminalis (Manna Gum) leaves. Subsequent statistical analysis showed differences between antimicrobial and anti-QS activities, whereas both activities were defined by phylogenetic position of medical resource plant. Finally, extract from Quercus robur cortex revealed at least two fractions, showing different anti-QS mechanisms. These data confirm that multicomponent anti-infectious mechanisms are used by plants, which may be useful for drug development
1. A. J. Alanis, Resistance to antibiotics: are we in the post-antibiotic era? Arch. Med. Res. 36 (2005) 697-705; DOI: 10.1016/j.arcmed.2005.06.009.
2. T. Bjarnsholt and M. Givskov, Quorum sensing inhibitory drugs as next generation antimicrobials: worth the effort? Curr. Infect. Dis. Rep. 10 (2008) 22-28; DOI: 10.1007/s11908-008-0006-y.
3. M. Hentzer and M. Givskov, Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections, J. Clin. Invest. 112 (2003) 1300-1307; DOI: 10.1172/ JCI200320074.
4. M. C. Marjorie, Plant products as antimicrobial agents, Clin. Microbiol. Rev. 4 (1999) 564-582.
5. D. Trombetta, F. Castelli, M. G. Sarpietro, V. Venuti, M. Cristani, C. Daniele, A. Saija, G. Mazzanti and G. Bisignano, Mechanisms of antibacterial action of three monoterpenes, Antimicrob. Agents Chemother. 49 (2005) 2474-2478; DOI: 10.1128/AAC.49.6.2474-2478.2005.
6. W. C. Fuqua, S. C. Winans and E. P. Greenberg, Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators, J. Bacteriol. 176 (1994) 269-275.
7. N. A. Whitehead, A. M. Barnard, H. Slater, N. J. Simpson and G. P. Salmond, Quorum-sensing in Gram-negative bacteria, FEMS Microbiol. Rev. 25 (2001) 365-404.
8. C. M. Waters and B. L. Bassler, Quorum-sensing: cell-to-cell communication in bacteria, Annu. Rev. Cell Dev. Biol. 21 (2005) 319-346.
9. M. B. Miller and B. L. Bassler, Quorum sensing in bacteria, Annu. Rev. Microbiol. 55 (2001) 165-199.
10. P. Williams, Quorum sensing, communication and cross kingdom signalling in the bacterial world, Microbiology 153 (2007) 3923-3938; DOI: 10.1099/mic.0.2007/012856-0.
11. M. Teplitski, J. B. Robinson and W. D. Bauer, Plants secrete substances that mimic bacterial N-acyl homoserine lactone signal activities and affect population density-dependent behaviours in associated bacteria, Mol. Plant-Microbe Inter. 13 (2000) 637-648.
12. M. Manefield, T. B. Rasmussen, M. Henzter, J. B. Andersen, P. Steinberg, S. Kjelleberg and M. Givskov, Halogenated furanones inhibit quorum sensing through accelerated LuxR tumover, Microbiology 148 (2002) 1119-1127.
13. A. L. Adonizio, K. Downum, B. C. Bennett and K. Mathee, Anti-quorum sensing activity of medicinal plants in southern Florida, J. Ethnopharmacol. 105 (2006) 427-435; DOI: 10.1016/j.jep.2005.11. 025.
14. M. Zahin, S. Hasan, F. Aqil, M. S. A. Khan, F. M. Husain and I. Ahmad, Screening of certain medicinal plants from India for their anti-quorum sensing activity, Indian J. Exp. Biol. 48 (2010) 1219-1224.
15. H. Liu, S. J. Coulthurst, L. Pritchard, P. E. Hedley, M. Ravensdale, S. Humphris, T. Burr, G. Takle, M. B. Brurberg, P. R. Birch, G. P. Salmond and I. K. Toth, Quorum sensing coordinates brute force and stealth modes of infection in the plant pathogen Pectobacterium atrosepticum, PLoS Pathog. 4 (2008) 1-11; DOI: 10.1371/journal.ppat.1000093.
16. R. Al-Hussaini and A. M. Mahasneh, Microbial growth and Quorum sensing antagonist activities of herbal plants extracts, Molecules 14 (2009) 3425-3435; DOI: 10.3390/molecules 14093425.
17. J. Lee, J. S. Kim, C. H. Nahm, J. W. Choi, J. Kim, S. H. Pai, K. H. Moon, K. Lee and Y. Chong, Two cases of Chromobacterium violaceum infection after injury in a subtropical region, J. Clin. Microbiol. 37 (1999) 2068-2070.
18. F. Fantinatti-Garboggini, R. de. Almeida, V. do. A. Portillo, T. A. P. Barbosa, P. B. Trevilato, C. E. R. Neto, R. D. Coelho, D. W. Silva, L. A. Bartoleti, E. S. Hanna, M. Brocchi and G. P. Manfio, Drug resistance in Chromobacterium violaceum, Genet. Mol. Res. 3 (2004) 134-147.
19. K. H. McClean, M. K. Winson, L. Fish, A. Taylor, S. R. Chhabra, M. Camara, M. Daykin, J. H. Lamb, S. Swift, B. W. Bycroft, G. S. Stewart and P. Williams, Quorum sensing and Chromobacterium violaceum: exploitation of violacein production and inhibition for the detection of N-acylhomoserine lactones, Microbiology 143 (1997) 3703-3711; DOI: 10.1099/00221287-143-12-3703.
20. R. S. Blosser and K. M. Gray, Extraction of violacein from Chromobacterium violaceum provides a new quantitative bioassay for N-acylhomoserine lactone autoinducers, J. Microbiol. Methods 40 (2000) 47-55.
21. P. R. August, T. H. Grossman, C. Minor, M. P. Draper, I. A. MacNeil, J. M. Pemberton, K. M. Call, D. Holt and M. S. Osburne, Sequence analysis and functional characterization of the violacein biosynthetic pathway from Chromobacterium violaceum, J. Mol. Microbiol. Biotechnol. 2 (2000) 513-519.
22. T. Hoshino, Violacein and related tryptophan metabolites produced by Chromobacterium violaceum: biosynthetic mechanism and pathway for construction of violacein core, Appl. Microbiol. Biotechnol. 91 (2011) 1463-1475; DOI: 10.1007/s00253-011-3468-z.
23. A. Vieira, A comparison of traditional anti-inflammation and anti-infection medicinal plants with current evidence from biomedical research: Results from a regional study, Pharmacognosy Res. 2 (2010) 293-295; DOI: 10.4103/0974-8490.72326.
24. V. Huerta, K. Mihalik, S. H. Crixell and D. A. Vattem, Herbs, spices and medicinal plants used in Hispanic traditional medicine can decrease quorum sensing dependent virulence in Pseudomonas aeruginosa, Int. J. Appl. Res. Nat. Prod. 1 (2008) 9-15.
25. C.-H. Yang and Y.-H. Li, Chromobacterium violaceum infection: A clinical review of an important but neglected infection, J. Chin. Med. Assoc. 74 (2011) 435-441; DOI: 10.1016/j.jcma.2011.08.013.
26. F. Perez-Montano, I. Jimenez-Guerrero, R. C. Sanchez-Matamoros, F. J. Lopez-Baena, F. J. Ollero, M. A. Rodriguez-Carvajal, R. A. Bellogin and M. R. Espuny, Rice and bean AHL-mimic quorum- sensing signals specifically interfere with the capacity to form biofilms by plant-associated bacteria, Res. Microbiol. 164 (2013) 749-760; DOI: 10.1016/j.resmic.2013.04.001.
27. K. Duric, E. Kovac-Besovic, H. Niksic and E. Sofic, Antibacterial activity of methanolic extracts, decoction and isolated triterpene products from different parts of birch, Betula pendula, Roth, J. Plant Stud. 2 (2013) 61-70.
28. M. A. Szabo, G. Z. Varga, J. Hohmann, Z. Schelz, E. Szegedi, L. Amaral and J. Molnar, Inhibition of quorum-sensing signals by essential oils, Phytother. Res. 24 (2010) 782-786.
29. S. Kokkiligadda, P. A. Karlapudi, M. Indira and V. P. Kodali. Biochemical and molecular characterization of biofilm producing bacteria, Int. J. Pharm. Biol. Sci. 4 (2013) 702-712.
30. A. L. Adonizio, J. Dawlaty, F. M. Ausubel, J. Clardy and K. Mathee, 7th Joint Meeting of GA, AFERP, ASP, PSER & SIF, Athens (Greece), August 3-8, 2008; Ellagitannins from Conocarpus erectus exhibit anti-quorum sensing activity against Pseudomonas aeruginosa, Planta Med. 74 (2008); DOI: 10.1055/s-0028-1084373.
31. Angiosperm Phylogeny Group, An update of the angiosperm phylogeny group classification for the orders and families of flowering plants: APG III, Bot. J. Linn. Soc. 161 (2009) 105-121; DOI: 10.1111/j.1095-839.2009.00996.x.