gidaveyem Gıda ve Yem Bilimi Teknolojisi Dergisi 1303-3107 2822-2873 GIDA VE YEM KONTROL MERKEZ ARAŞTIRMA ENSTİTÜSÜ MÜDÜRLÜĞÜ Pseudomonas aeruginosa: Özellikleri ve Quorum Sensing Mekanizması Sırıken Belgin Ondokuz Mayıs Üniversitesi, Veteriner Fakültesi, Su Ürünleri Hastalıkları Anabilim Dalı Öz Veli Altınordu İlçe Gıda Tarım ve Hayvancılık Müdürlüğü/ORDU Özet Pseudomonas 09 01 2017 0 18 42 52 07 07 2017 08 01 2017 Copyright © 2015, Gıda ve Yem Bilimi Teknolojisi Dergisi 2015 Gıda ve Yem Bilimi Teknolojisi Dergisi

Pseudomonas aeruginosa fırsatçı bir mikroorganizma olup, gıdalara ve gıda ile temas eden yüzeylerdetutunup, biyofilm oluşturabilme kabiliyetine sahip mikroorganizmaların başında gelmektedir. Etken çoğunluklanosokomiyal ve immun sistemi baskılanmış konakçılarda enfeksiyonlara neden olur. Etkenin biyofilm içindeüremesi ve antibiyotik dirençliliği nedeniyle eredikasyonu güçtür. Enfeksiyonun oluşumu sırasında,P. aeruginosa Quorum sensing (QS-Çevreyi Algılama) regülatör sisteminin kontrolü altında bir dizi virulansfaktörler üretir. QS; bakterilerin biyofilm oluşturabilmek amacıyla bitişiğinde yer alan diğer bakteri hücrelerinesinyal molekülleri (oto-induser-AI) göndererek hücreleri uyarması ve etkileşime geçmesine verilen isimdir. Bunedenle ekstrasellüler sinyaller ve QS düzenleme sistemleri biyofilm varlığı için oldukça önemli olup, yenitedavi edici stratejilerin gelişmesi için de etkili bir hedef olarak düşünülmektedir. P. aeruginosa’da QSdüzenlenmesi en az iki N-asetil homoserin lakton kodlayan gen çiftleri (LasI–RhII) tarafından kontroledilmektedir. Bu genler aynı zamanda elastaz, alkalin fosfataz, hidrojen siyanid, ekzotoksin A, katalaz,ramnolipid, piyosiyanin, asile edilmiş homoserin laktonları ve superoksit dizmutaz gibi virulans faktörlerinüretimini de düzenlerler. QS’yi düzenlemede yardımcı olan bir diğer gen çifti ise PQS-MvfR’dir. PQSekspresyonu LasR’ye bağlıdır ve Rh1R geni ekspresyonunu artırır.

 P. aeruginosa Virulans Faktörleri Biyofilm Abdel-Mawgoud, A.M., Lepine, F. ve Deziel, E., 2010. Rhamnolipids: Diversity of structures, microbial origins and roles. Applied Microbiology and Biotechnology, 86: 1323-1336. Arevalo-Ferro, C. Hentzer, M., Reil, G., Görg, A., Kjelleberg, S., Givskov, M., Riedel, K. ve Eberl, L., 2003. Identification of quorum-sensing regulated, proteins in the opportunistic pathogen Pseudomonas aeruginosa by proteomics. Environmental Microbiology (12):1350-69. Alcorn, J.F. ve Wright, J.R., 2004. Degradation of pulmonary surfactant protein D by Pseudomonas aeruginosa elastase abrogates innate immune function. The Journal of Biological Chemistry, 279:30871-30879. Baron E. ve Finegold, S.,1986. Bailey and Scott’s Diagnostic Microbiology. Mosby Co, 7th ed, 422-424 s 16. St Louis. Ben Haj Khalifa, A., Moissenet, D., Vu Thien, H. ve Khedher, M., 2011. Virulence factors in Pseudomonas aeruginosa: mechanisms and modes of regulation. Annales de biologie clinique (Paris),69(4),393–403. Bilgehan H., 2000. Non-fermentatif gram olumsuz basiller. Editör: Bilgehan H. Klinik Mikrobiyoloji, Fakülteler Kitabevi Barış Yayınları, s 175-197, İzmir. Boyd, A. ve Chakrabarty, A.M., 1995. Pseudomonas aeruginosa biofilms: role of the alginate exopolysaccharide. Journal of Industrial Microbiology,15:162-168. Britigan, B.E., Railsback, M.A. ve Cox, C.D., 1999. The Pseudomonas aeruginosa secretory product pyocyanin inactivates alpha1 rotease inhibitor: implications for the pathogenesis of cystic fibrosis lung disease. Infection and immunity, 67(3):1207–12. Case, R.J., Labbate, M. ve Kjelleberg, S., 2008. AHL-driven quorum-sensing circuits: their frequency and function among the Proteobacteria. The ISME Journal, 2: 345–349. Costerton, J.W., Montanaro, L. ve Arciola, C.R., 2004. Biofilm in implant infections: its production and regulation. Int. Journal of Artificial Organs, 28:1062-1068. Costerton, J.W., Stewart, P.S. ve Greenberg, E.P., 1999. “Bacterial biofilms: A common cause of persistent infections,” Science, 284: 1318-1322. Davies, D., 2003. Understanding biofilm resistance to antibacterial agents. Nature Reviews Drug Discovery, 2 (2):114-122. Delden, C.V. ve Iglewski, B.H., 1998. Cell-to-cell signalling and Pseudomonas aeruginosa infections. Emerging Infectious Diseases Journal, 4: 551-9. Denton, M. ve Wilcox, M.H., 1997. Antimicrobial treatment of pulmonary colonazation and infection by Pseudomonas aeruginosa in cystic fibrosis patients. Journal of Antimicrobial Chemotheraphy, 40:468-474. Denning, G.M., Wollenweber, L.A., Railsback, M.A., Cox, C.D., Stoll, L.L. ve Britigan, BE.,1998. Pseudomonas pyocyanin increases interleukin-8 expression by human airway epithelial cells. Infection and immunity, 66 (12):5777–84. Donabedian, H., 2003. Quorum sensing and its relevance to infectious diseases. Journal of Infection, 46: 207-214. Dong, Y.H. ve Zhang, L.H., 2005. Quorum sensing and quorum quenching enzymes. Journal of Microbiology, 43:101-9. Donlan, R.M., 2002. Biofilms: Microbial life on surfaces. Emerging Infectious Diseases, 8:881-890. Dunne, Jr. W.M., 2002. Bacterial adhesion: seen any good biofilms lately? Clinical Microbiology Reviews,15:155-166. Erdem, B., 1999. Pseudomonaslar. Ed:Ustaçelebi Ş. ve ark, Temel ve Klinik Mikrobiyoloji, Güneş Kitabevi, s 551-566, Ankara, Türkiye. Fuqua, C., Parsek, M.R. ve Greenberg, E.P., 2001. Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing. Annual Review of Genetics, 35:439-468. Bilgin SARIKEN, Veli ÖZ / Gıda ve Yem Bilimi - Teknolojisi Dergisi / Journal of Food and Feed Science - Technology 18:49-52 (2017/2) 49 Gambello, M.J., Kaye, S. ve Iglewski, B.H., 1993. LasR of Pseudomonas aeruginosa is a transcriptional activator of the alkaline protease gene (apr) and an enhancer of exotoxin A expression. Infection and Immunity, 61:1180–1184. Girard, G. ve Bloemberg, G., 2008. Central role of quorum sensing in regulating the production of pathogenicity factors in Pseudomonas aeruginosa. Future Microbiology,3 (1): 97-106. Guerra-Santos, L.H., Kappeli, O. ve Fiechter, A., 1986. Dependence of Pseudomonas aeruginosa continuous culture biosurfactant production on nutritional and environmental factors. Applied Microbiology and Biotechnology, 24:443-448. Hall-Stoodley, L., Costerton, J.W. ve Stoodley, P., 2004. Bacterial biofilms: from the natural environment to infectious diseases. Nature Reviews Microbiology, 2:95-108. Hassan, A., Usman, J., Kaleem, F., Omair, M., Khalid, A. ve Iqbal, M., 2011. Evaluation of different detection methods of biofilm formation in the clinical isolates. Brazilian Journal of Infectious Diseases,15(4):305–11. Hauser, A.R., 2009. The type III secretion system of Pseudomonas aeruginosa: infection by injection. Nature Reviews Microbiology, 7 (9): 654-665. Jarvis, F. G., ve Johnson, M.J., 1949. A glyco-lipid produced by Pseudomonas aeruginosa. Journal of American Chemistry Society, 71:4124-4126. Karatuna, O. ve Yağcı, A., 2008. Pseudomonas aeruginosa’da virülans faktörleri ve quorum sensing. Türk Mikrobioloji Cemiyeti Dergisi, 38: 42-51. Kennedy, P. ve Brammah, S., Wills, Burns,E., 2010. biofilm and a new appraisal of burn wound sepsis. Burns 36:49. Kim, E.J., Wang, W., Deckwer, W.D., ve Zeng, A.P., 2005. Expression of the quorum-sensing regulatory protein LasR is strongly affected by iron and oxygen concentrations in cultures of Pseudomonas aeruginosa irrespective of cell density. Microbiology (Reading, England). 151(Pt 4):1127–38. King, A. ve Philips, I., 1978.“ The Identification of Pseudomonas and Related Bacteria in a Clinical Microbiology”, I. Medical Microbiology, 11:165-175. Kipnis, E., Sawa, T., Wiener-Kronish, J., 2006. Targeting Mechanisms of Pseudomonas aeruginosa pathogenesis. Medecine Et Maladies Infectieuses, 36:78-91. Lagournintzis, G., Christofidou, M., Ditnitracopoulos, G. Ve Paliogianni, F., 2003. Pseudomonas aeruginosa slime glycolipoprotein is a potent stimulant of 67 tumor necrosis factor alpha gene expression and activation of transcription activators nuclear factor kappa B and activator protein 1 in human monocytes. Infection and Immunity, 71 (8): 4614-4622. Lang, S., ve Wullbrandt, D., 1999. Rhamnose lipids—biosynthesis, microbial production and application potential. Applied Microbiology and Biotechnology, 51:22-32. Lau, G.W., Hassett, D.J., Ran, H., ve Kong, F., 2004. The role of pyocyanin in Pseudomonas aeruginosa infection. Trends of Molecular Medicine,10(12):599-606. Lederberg, J., 2000. Pseudomonas. Encyclopedia of Microbiology. Second Edition. Volume 3., 2000. p. 876-891. San Diego, USA. Maçin, S., 2014. Pigmentli Ve Pigmentsiz Pseudomonas aerugınosa Suşlarının Virulans Faktörlerinin Fenotipik Ve Genotipik Olarak Karşılaştırılması. T.C. Hacettepe Üniversitesi Tıp Fakültesi Tıbbi Mikrobiyoloji Anabilim Dalı, Uzmanlık Tezi, Ankara. Malloy, J.L., Veldhuizen, R.A.W., Thibodeaux, B.A., O’ Callaghan, R.J. ve Wright, J.R., 2005. Pseudomonas aeruginosa protease IV degrades surfactant proteins and inhibits surfactant host defense and biophysical functions. American Journal Physology Lung Cellular and Molecular Physiology, 288: 409-418. Marshall, K.C., 1976. Interfaces in microbial ecology, Harvard University Press, Cambridge, MA. pp. 44-47. Meyer, J.M., 2000. Pyoverdines: pigments, siderophores and potential taxonomic markers of fluorescent Pseudomonas species. Archives of Microbiology, 174 (3): 135-142. Mitov, I., Strateva, T., ve Markova, B., 2010. Prevalence of Virulence Genes among Bulgarian Nosocomial and Cystic Fibrosis Isolates of Pseudomonas Aeruginosa. Brazilian Journal of Microbiology, 41 (3), 588-595. Moore, E.R.B., Tindall, B.J., Martins dos Santos, V.AP., Pieper, D.H., Ramos, J-L., ve Palleroni, N.J.,2006. Nonmedical: Pseudomonas Chapter 3..3.21. Prokaryotes 6: 646-703. Muller, M., 2006. Premature cellular senescence induced by pyocyanin, a redox-active Pseudomonas aeruginosa toxin. Free Radical Biology & Medicine, 41(11):1670–7. Nouraldin, A.A.M., Baddaour, M.M., Harfous, A.H., ve Essa, A.A.M., 2016. Bacteriophage-antibiotic synergism to control planktonic and biofilm producing clinical isolates of Pseudomonas aeruginosa. Alexandria Journal of Medicine, 52 (2); 99-105. Nicas, T.I. ve Iglewski, B.H, 1985. The Contribution of Exoproducts to Virulence of Pseudomonas-Aeruginosa. Can J Microbiol, 31 (4), 387-392. 68 Novick, R.P. ve Muir, W.M., 1999. Virulence gene regulation by peptides in staphylococci and other Grampositive bacteria. Current Opinion in Microbiology,2:40-45. O'May, C.Y., Sanderson, K., Roddam, L.F., Kirov, S.M. ve Reid, D.W., 2009. Iron-binding compounds impair Pseudomonas aeruginosa biofilm formation, especially under anaerobic conditions. Journal of Medical Microbiology, 58(Pt 6):765–73. Pesci, E.C., Milbank, J.B., Pearson, J.P., McKnight, S., Kende, A.S., Greenberg, E.P. ve Iglewski, B.H., 1999. Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa. Proceedings of the National Academy of Sciences USA, 28;96(20):11229-34. Post, J.C., Stoodley, P., Hall-Stoodley, L. ve Ehrlich, G.D., 2004. The role of biofilms in otolaryngologic infections. Curr Opin Otolaryngol Head Neck Surgery, 12:185-190. Rasamiravaka, T., Labtani, Q., Duez P. ve El Jaziri, M., 2015. The Formation of Biofilms by Pseudomonas aeruginosa: A Review of the Natural and Synthetic Compounds Interfering with Control Mechanisms. BioMed Research International, Volume 2015, Article ID 759348, 17 pages. Romero, M.C., Cazau, M.C., Giorgieri, S. ve Arambarri, A.M., 1998. Phenantrene degradation by microorganisms isolated from a contaminated stream. Environmental Pollutin, 101: 355-359. Ruby, E.G., 1996. Lessons from a cooperative, bacterial-animal association: the Vibrio fischeri Euprymna scolopes light organ symbiosis. Annual Review of Microbiology, 50: 591–624. Salyers, A.A., ve Whitt, D.D., 1994. “Bacterial pathogenesis: A molecular approach,” American Society for Microbiology, 260-268. Shaver, C.M., ve Hauser, A.R., 2004. Relative contributions of Pseudomonas aeruginosa ExoU, ExoS, and ExoT to virulence in the lung. Infection and Immunity, 72 (12): 6969-6977. Shunmugaperumal, T., 2010. Biofilm Eraddication and Prevention: A Pharmaceutical Approach to Medical Device Infections, John Wiley & Sons, Inc. Schuster, M., Hawkins, A.C., Harwood, C.S., Greenberg, E.P., 2004. The Pseudomonas aeruginosa RpoS regulon and its relationship to quorum sensing. Molecular Microbiology, 51: 973–985. Smith, R.S., Harris, S.G., Phipps, R., Iglewski, B., 2002. The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl) homoserine lactone contributes to virulence and induces inflammation in vivo. Journal of Bacteriology, 184: 1132 Smith, R.S. ve Iglewski, B.H., 2003. “Pseudomonas aeruginosa quorum sensing as a potential antimicrobial target,” Journal of Clinical Investment, 112: 1460-1465. Stanier, R. Y., Palleroni, N. J., ve Doudoroff, M., 1966. The aerobic pseudomonads: a taxonomic study. Journal of Genetic Microbiolology, 43:159–271. Singh, P.K., Parsek, M.R., Greenberg, E.P. ve Welsh, M.J., 2002. A component of innate immunity prevents bacterial biofilm development. Nature, 417(6888):552–5. Song, Z., Kong, K.F., Wu, H., Maricic, B., Ramalingam, B., Priestap, H., Scheper, L., Quirke, J.M.E., Iby, N.H., ve Mathee, K., 2010. Panax ginseng has anti-inhibiting quorum sensing, a bacteria communication process critical for establishhing infectiion. Phytomedicine, 17; 1040-1046. Şahin, R., 2007. Staphylococcus auresus Suşlarında Biyofilm Üretimi, Biyofilm Pozitif ve Negatif Suşların Genotipik ve Fenotipik Karakterlerinin Karşılaştırılması. Pamukkale Üniversitesi Tıp Fakültesi Mikrobiyoloji ve Klinik Mikrobiyoloji Anabilim Dalı, Uzmanlık Tezi. Tormo, M.A., Martí, M., Valle, J., Manna, A.C., Cheung, A.L., Lasa, I., Penadés, J.R., 2005. SarA is an essential positive regulator of Staphylococcus epidermidis biofilm development. Journal of Bacteriology, 187(7):2348-56. Van Delden, C., ve Iglewski, B.H. 1998. Cell-to-cell signaling and Pseudomonas aeruginosa infections. Emerging Infectious Diseases, 4:551– 560. Vasil, M.L. ve Ochsner, U.A., 1999. The response of Pseudomonas aeruginosa to iron: genetics, biochemistry and virulence. Molecular Microbiology,34(3):399–413. Public Health England (UK Standards for Microbiology Investigations)., 2015. Identification of Pseudomonas species and other NonGlucose Fermenters. Issued by the Standards Unit, Microbiology Services. Public Health Services,3: 1- 41. Venturi, V., 2006. Regulation of quorum sensing in Pseudomonas. FEMS Microbiology Reviews, 30 (2), 274–291. Vuong C, Otto M., 2002. Staphylococcus epidermidis infections. Microbial Infection,4:481-489. Wiener-Kronish, J.P., Sakuma, T., Kudoh, I., 1993. Alveolar epithelial injury and pleural empyema in acute P. aeruginosa pneumonia in anesthetized rabbits. Journal of Appl Physiolology, 75(4):1661–1669 Wong, A.C.L., 1998. Biofilms in food processing environments. Journal of Dairy Science, 81:2765-2770. Woods, D.E., 2004. Comparative genomic analysis of Pseudomonas aeruginosa virulence. Trends Microbiology, 12 (10): 437-439. Wozniak, D.J., Wyckoff, T.J.O., Starkey, M., Keyser, R., Azadi, P., O'Toole, G.A. ve Parsek, M.R., 2003. Alginate is not a significant component of the extracellular polysaccharide matrix of PA14 and PAO1 Pseudomonas aeruginosa biofilms. Proceedings of the National Academy of Sciences USA, 100:7907–7912. Wu, L.R., Zaborina, O., Zaborin, A., Chang, E.B., Musch, M., Holbrook, C., Turner, J.R. ve Alverdy, J.C., 2005. “Surgical injury and metabolic stress enhance the virulence of the human opportunistic pathogen Pseudomonas aeruginosa,” Surgical Infection, 6: 185–195. Zhu, J. Ve Winans, S.C., 2001. The quorum-sensing transcriptional regulator TraR requires its cognate signaling ligand for protein folding, protease resistance, and dimerization. Proceedings of the National Academy of Sciences U S A, 98(4): 1507–1512.