Quorum sensing inhibition properties of lichen forming fungi extracts from Cetrelia species against Pseudomonas aeruginosa

Abstract

Communication among bacterial cells through quorum sensing (QS) system in Pseudomonas aeruginosa is responsible for antibiotic resistant infections in hospitals. This bacterium can regulate its virulence gene expressions through its QS systems. It is now known that inhibiting QS can leave bacteria vulnerable. Therefore, it is necessary to determine natural sources to obtain potential quorum sensing inhibitors. This study aims to investigate the QS inhibitor (QSI) bioactivity of the culture extracts obtained from lichen-forming fungi (LFF) of five Cetrelia species against P. aeruginosa. Extracts were applied to monitor strains and all samples have shown varying amounts of QS inhibition activity. Our study demonstrates that LFF cultures can be utilized to produce QSI compounds instead of collecting slow growing natural lichen thalli. We believe that this research will cast a new light on identification and isolation of active compounds from the extracts and assessment of their compatibility for future drug research.

Keywords

• quorum sensing
• Pseudomonas aeruginosa
• secondary metabolites
• lichen forming fungi

References

1. Ahmed, S. A., Rudden, M., Smyth, T. J., Dooley, J. S., Marchant, R., & Banat, I. M. (2019). Natural quorum sensing inhibitors effectively downregulate gene expression of Pseudomonas aeruginosa virulence factors. Applied Microbiology and Biotechnology, 103(8), 3521-3535.
2. Al-Ani, I., Zimmermann, S., Reichling, J., & Wink, M. (2015). Pharma-cological synergism of bee venom and melittin with antibiotics and plant secondary metabolites against multi-drug resistant microbial pathogens. Phytomedicine, 22(2), 245-255. doi:10.1016/j.phymed.2014.11.019
3. Azimi, H., Khakshur, A. A., Aghdasi, I., Fallah-Tafti, M., & Abdollahi, M. (2012). A review of animal and human studies for management of benign prostatic hyperplasia with natural products: perspective of new pharmacological agents. Inflamm Allergy Drug Targets, 11(3), 207-221. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22512478
4. Bjarnsholt, T., van Gennip, M., Jakobsen, T. H., Christensen, L. D., Jensen, P. O., & Givskov, M. (2010). In vitro screens for quorum sensing inhibitors and in vivo confirmation of their effect. Nature Protocols, 5(2), 282-293. doi:10.1038/nprot.2009.205
5. Ciofu, O., Tolker-Nielsen, T., Jensen, P. O., Wang, H., & Hoiby, N. (2015). Antimicrobial resistance, respiratory tract infections and role of biofilms in lung infections in cystic fibrosis patients. Advanced Drug Delivery Reviews, 85, 7-23. doi:10.1016/j.addr.2014.11.017
6. De Kievit, T. (2009). Quorum sensing in Pseudomonas aeruginosa biofilms. Environmental Microbiology, 11(2), 279-288.
7. Diggle, S. P., Winzer, K., Chhabra, S. R., Chlshabra, S. R., Worrall, K. E., Camara, M., & Williams, P. (2003). The Pseudomonas aeruginosa quinolone signal molecule overcomes the cell density-dependency of the quorum sensing hierarchy, regulates rhl-dependent genes at the onset of stationary phase and can be produced in the absence of LasR. Molecular Microbiology, 50(1), 29-43. doi:10.1046/j.1365-2958.2003.03672.x
8. Fernández-Moriano, C., Divakar, P. K., Crespo, A., & Cuadrado, M. P. G.-S. (2015). Antioxidant and cytoprotective potentials of Par-meliaceae lichens and identification of active compounds. Anales de la Real Academia Nacional de Farmacia, 81, 164-178.

9. Gokalsin, B., & Sesal, N. C. (2016). Lichen secondary metabolite ever-nic acid as potential quorum sensing inhibitor against Pseudomonas aeruginosa. World Journal of Microbiology and Biotechnology, 32(9), 150. doi:10.1007/s11274-016-2105-5
10. Gokalsin, B., Berber, D., Ozyigitoglu, G. C., Yesilada, E., & Sesal, N. C. (2019). Quorum sensing attenuation properties of ethnobotanically valuable lichens against Pseudomonas aeruginosa. Plant Biosystems-An International Journal Dealing with all Aspects of Plant Biology, 1-8.
11. Hancock, R. E., & Speert, D. P. (2000). Antibiotic resistance in Pseudo-monas aeruginosa: mechanisms and impact on treatment. Drug Re-sist Updat, 3(4), 247-255. doi:10.1054/drup.2000.0152
12. Hentzer, M., Eberl, L., Nielsen, J., & Givskov, M. (2003). Quorum sensing - A novel target for the treatment of biofilm infections. Bio-drugs, 17(4), 241-250. doi:Doi 10.2165/00063030-200317040-00003
13. Hentzer, M., Riedel, K., Rasmussen, T. B., Heydorn, A., Andersen, J. B., Parsek, M. R., . . . Givskov, M. (2002). Inhibition of quorum sens-ing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology-Sgm, 148, 87-102.
14. Jakobsen, T. H., Bjarnsholt, T., Jensen, P. O., Givskov, M., & Hoiby, N. (2013). Targeting quorum sensing in Pseudomonas aeruginosa bio-films: current and emerging inhibitors. Future Microbiology, 8(7), 901-921. doi:10.2217/fmb.13.57
15. Jones, R. N., Stilwell, M. G., Rhomberg, P. R., & Sader, H. S. (2009). Anti pseudomonal activity of piperacillin/tazobactam: more than a decade of experience from the SENTRY Antimicrobial Surveillance Program (1997-2007). Diagnostic Microbiology and Infectious Disease, 65(3), 331-334. doi:10.1016/j.diagmicrobio.2009.06.022
16. Kostylev, M., Kim, D. Y., Smalley, N. E., Salukhe, I., Greenberg, E. P., & Dandekar, A. A. (2019). Evolution of the Pseudomonas aerugino-sa quorum-sensing hierarchy. Proceedings of the National Academy of Sciences, 116(14), 7027-7032.
17. Lal, B., & Upreti, D. K. (1995). Ethnobotanical Notes on Three Indian Lichens. The Lichenologist, 27(1), 77-79. doi:10.1006/lich.1995.0006
18. Lambert, M. L., Suetens, C., Savey, A., Palomar, M., Hiesmayr, M., Morales, I., . . . Wolkewitz, M. (2011). Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study. Lancet In-fect Dis, 11(1), 30-38. doi:10.1016/S1473-3099(10)70258-9
19. Li, T., Cui, F., Bai, F., Zhao, G., & Li, J. (2016). Involvement of acy-lated homoserine lactones (AHLs) of Aeromonas sobria in spoilage of refrigerated turbot (Scophthalmus maximus L.). Sensors, 16(7), 1083.
20. Malhotra, S., Subban, R., & Singh, A. (2008). Lichens-role in traditional medicine and drug discovery. The Internet Journal of Alternative Medicine, 5(2), 151-170.
21. McGrath, S., Wade, D. S., & Pesci, E. C. (2004). Dueling quorum sens-ing systems in Pseudomonas aeruginosa control the production of the Pseudomonas quinolone signal (PQS). Fems Microbiology Let-ters, 230(1), 27-34. doi:10.1016/S0378-1097(03)00849-8
22. Molnar, K., & Farkas, E. (2010). Current results on biological activities of lichen secondary metabolites: a review. Zeitschrift für Naturforschung C, 65(3-4), 157-173. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20469633
23. Pachori, P., Gothalwal, R., & Gandhi, P. (2019). Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit; a critical review. Genes & Diseases, 6(2), 109-119.
24. Paczkowski, J. E., Mukherjee, S., McCready, A. R., Cong, J. P., Aquino, C. J., Kim, H., ... & Bassler, B. L. (2017). Flavonoids suppress Pseudomonas aeruginosa virulence through allosteric inhibition of quorum-sensing receptors. Journal of Biological Chemistry, 292(10), 4064-4076.
25. Savale, S. A., Pol, C. S., Khare, R., Verma, N., Gaikwad, S., Mandal, B., & Behera, B. C. (2016). Radical scavenging, prolyl endopeptidase inhibitory, and antimicrobial potential of a cultured Himalayan lichen Cetrelia olivetorum. Pharmaceutical Biology, 54(4), 692-700. doi:10.3109/13880209.2015.1072567
26. Savo, V., Joy, R., Caneva, G., & McClatchey, W. C. (2015). Plant selection for ethnobotanical uses on the Amalfi Coast (Southern Italy). Journal of Ethnobiology and Ethnomedicine, 11, 58. doi:10.1186/s13002-015-0038-y
27. Shrestha, G. (2015). Exploring the antibacterial, antioxidant, and anti-cancer properties of lichen metabolites, Doctoral Dissertation, (pp. 1-116). Brigham Young University, Provo, USA.
28. Shukla, V., Joshi, G. P., & Rawat, M. (2010). Lichens as a potential natural source of bioactive compounds: a review. Phytochemistry Reviews, 9(2), 303-314.
29. Truchado, P., Tomas-Barberan, F. A., Larrosa, M., & Allende, A. (2012). Food phytochemicals act as Quorum Sensing inhibitors re-ducing production and/or degrading autoinducers of Yersinia entero-colitica and Erwinia carotovora. Food Control, 24(1-2), 78-85. doi:10.1016/j.foodcont.2011.09.006
30. Yamamoto, Y. (2002). Discharge and germination of lichen ascospores in the laboratory. Lichenology, 1, 11-22.
31. Yamamoto, Y., Hara, K., Kawakami, H., & Komine, M. (2015). Lichen Substances and Their Biological Activities. In Recent Advances in Lichenology (pp. 181-199): Springer.
32. Yang, L., Rybtke, M. T., Jakobsen, T. H., Hentzer, M., Bjarnsholt, T., Givskov, M., & Tolker-Nielsen, T. (2009). Computer-Aided identi-fication of recognized drugs as Pseudomonas aeruginosa quorum-sensing inhibitors. Antimicrobial Agents and Chemotherapy, 53(6), 2432-2443. doi:10.1128/Aac.01283-08
33. Zeng, Z., Qian, L., Cao, L., Tan, H., Huang, Y., Xue, X., . . . Zhou, S. (2008). Virtual screening for novel quorum sensing inhibitors to eradicate biofilm formation of Pseudomonas aeruginosa. Applied Microbiology and Biotechnology, 79(1), 119-126. doi:10.1007/s00253-008-1406-5