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2016 | 63 | 3 | 427-436
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Characterization of the interactions between human high-molecular-mass kininogen and cell wall proteins of pathogenic yeasts Candida tropicalis

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Candida tropicalis is one of the most frequent causes of serious disseminated candidiasis in human patients infected by non-albicans Candida species, but still relatively little is known about its virulence mechanisms. In our current study, the interactions between the cell surface of this species and a multifunctional human protein - high-molecular-mass kininogen (HK), an important component of the plasma contact system involved in the development of the inflammatory state - were characterized at the molecular level. The quick release of biologically active kinins from candidal cell wall-adsorbed HK was presented and the HK-binding ability was assigned to several cell wall-associated proteins. The predicted hyphally regulated cell wall protein (Hyr) and some housekeeping enzymes exposed at the cell surface (known as "moonlighting proteins") were found to be the major HK binders. Accordingly, after purification of selected proteins, the dissociation constants of the complexes of HK with Hyr, enolase, and phosphoglycerate mutase were determined using surface plasmon resonance measurements, yielding the values of 2.20 × 10-7 M, 1.42 × 10-7 M, and 5.81 × 10-7 M, respectively. Therefore, in this work, for the first time, the interactions between C. tropicalis cell wall proteins and HK were characterized in molecular terms. Our findings may be useful for designing more effective prevention and treatment approaches against infections caused by this dangerous fungal pathogen.
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  • Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland
  • Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland
  • Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland
  • Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland
  • Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland
  • Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland
  • Department of Structural Biology, Malopolska Centre of Biotechnology, Jagiellonian University in Krakow, Kraków, Poland
  • Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland
  • Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Kraków, Poland
  • Arendrup MC (2013) Candida and candidaemia. Susceptibility and epidemiology. Dan Med J 60: B4698.
  • Barbasz A, Guevara-Lora I, Rapala-Kozik M, Kozik A (2008) Kininogen binding to the surfaces of macrophages. Int Immunopharmacol 8: 211-216.
  • Ben Nasr A, Herwald H, Müller-Esterl W, Björck L (1995) Human kininogens interact with M protein, a bacterial surface protein and virulence determinant. Biochem J 305: 173-180.
  • Ben Nasr A, Herwald H, Sjöbring U, Renné T, Müller-Esterl W, Björck L (1997) Absorption of kininogen from human plasma by Streptococcus pyogenes is followed by the release of bradykinin. Biochem J 326: 657-660.
  • Ben Nasr A, Olsén A, Sjöbring U, Müller-Esterl W, Björck L (1996) Assembly of human contact phase proteins and release of bradykinin at the surface of curli-expressing Escherichia coli. Mol Microbiol 20: 927-935.
  • Bhoola KD, Figueroa CD, Worthy K (1992) Bioregulation of kinins: kallikreins, kininogens and kininases. Pharmacol Rev 44: 1-80.
  • Bouchara JP, Tronchin G, Annaix V, Robert R, Senet JM (1990) Laminin receptors on Candida albicans germ tubes. Infect Immun 58: 48-54.
  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254.
  • Bras G, Bochenska O, Rapala-Kozik M, Guevara-Lora I, Faussner A, Kozik A (2012) Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg(9)-Met-Lys-bradykinin. Biol Chem 393: 829-839. doi: 10.1515/hsz-2012-0157.
  • Butler G, Rasmussen MD, Lin MF, Santos MA, Sakthikumar S et al. (2009) Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459: 657-662. doi: 10.1038/nature08064.
  • Calixto JB, Cabrini DA, Ferreira J, Campos MM (2001) Inflammatory pain: kinins and antagonists. Curr Opin Anaesthesiol 14: 519-526.
  • Chai LY, Denning DW, Warn P (2010) Candida tropicalis in human disease. Crit Rev Microbiol 36: 282-298. doi: 10.3109/1040841X.2010.489506.
  • Chaudhary U, Goel S, Mittal S (2015) Changing trends of Candidemia and antifungal susceptibility pattern in a tertiary health care centre. Infect Disord Drug Targets 15: 171-176.
  • Colman RW, Schmaier AH (1997) Contact system: a vascular biology modulator with anticoagulant, profibrinolytic, antiadhesive, and proinflammatory attributes. Blood 90: 3819-3843.
  • Couture R, Harrisson M, Vianna RM, Cloutier F (2001) Kinin receptors in pain and inflammation. Eur J Pharmacol 429: 161-176.
  • Dühring S, Germerodt S, Skerka C, Zipfel PF, Dandekar T, Schuster S (2015) Host-pathogen interactions between the human innate immune system and Candida albicans - understanding and modeling defense and evasion strategies. Front Microbiol 6: 625. doi: 10.3389/fmicb.2015.00625.
  • Fernández-Ruiz M, Puig-Asensio M, Guinea J, Almirante B, Padilla B, Almela M, Díaz-Martín A, Rodríguez-Baño J, Cuenca-Estrella M, Aguado JM; CANDIPOP Project; GEIH-GEMICOMED (SEIMC); REIPI (2015) Candida tropicalis bloodstream infection: Incidence, risk factors and outcome in a population-based surveillance. J Infect 71: 385-394. doi: 10.1016/j.jinf.2015.05.009.
  • Giri S, Kindo A J (2012) A review of Candida species causing blood stream infection. Indian J Med Microbiol 30: 270-278. doi: 10.4103/0255-0857.99484.
  • Horn DL, Neofytos D, Anaissie EJ, Fishman JA, Steinbach WJ, Olyaei AJ, Marr KA, Pfaller MA, Chang CH, Webster KM (2009) Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin Infect Dis 48: 1695-1703.
  • Hoyer LL, Fundyga R, Hecht JE, Kapteyn JC, Klis FM, Arnold J (2001) Characterization of agglutinin-like sequence genes from non - albicans Candida and phylogenetic analysis of the ALS family. Genetics 157: 1555-1567.
  • Jong AY, Chen SH, Stins MF, Kim KS, Tuan TL, Huang SH (2003) Binding of Candida albicans enolase to plasmin(ogen) results in enhanced invasion of human brain microvascular endothelial cells. J Med Microbiol 52: 615-622.
  • Kapteyn JC, Hoyer LL, Hecht JE, Müller WH, Andel A, Verkleij AJ, Makarow M, Van Den Ende H, Klis FM (2000) The cell wall architecture of Candida albicans wild-type cells and cell wall-defective mutants. Mol Microbiol 35: 601-611.
  • Karkowska-Kuleta J, Kedracka-Krok S, Rapala-Kozik M, Kamysz W, Bielinska S, Karafova A, Kozik A (2011) Molecular determinants of the interaction between human high molecular weight kininogen and Candida albicans cell wall: Identification of kininogen-binding proteins on fungalcell wall and mapping the cell wall-binding regions on kininogen molecule. Peptides 32: 2488-2496.
  • Karkowska-Kuleta J, Kozik A (2014) Moonlighting proteins as virulence factors of pathogenic fungi, parasitic protozoa and multicellular parasites. Mol Oral Microbiol 29: 270-283. doi: 10.1111/omi.12078.
  • Karkowska-Kuleta J, Kozik A, Rapala-Kozik M (2010) Binding and activation of the human plasma kinin-forming system on the cell walls of Candida albicans and Candida tropicalis. Biol Chem 391: 97-103. doi: 10.1515/BC.2009.145.
  • Karkowska-Kuleta J, Zajac D, Bochenska O, Kozik A (2015) Surfaceome of pathogenic yeasts, Candida parapsilosis and Candida tropicalis, revealed with the use of cell surface shaving method and shotgun proteomic approach. Acta Biochim Pol 62: 807-819. doi: 10.18388/abp.2015_1140.
  • Kothavade RJ, Kura MM, Valand AG, Panthaki MH (2010) Candida tropicalis: its prevalence, pathogenicity and increasing resistance to fluconazole. J Med Microbiol 59: 873-880. doi: 10.1099/jmm.0.013227-0.
  • Kozik A, Karkowska-Kuleta J, Zajac D, Bochenska O, Kedracka-Krok S, Jankowska U, Rapala-Kozik M (2015) Fibronectin-, vitronectin- and laminin-binding proteins at the cell walls of Candida parapsilosis and Candida tropicalis pathogenic yeasts. BMC Microbiol 15: 197. doi: 10.1186/s12866-015-0531-4.
  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680-685.
  • Lee PY, Gam LH, Yong VC, Rosli R, Ng KP, Chong PP (2014) Immunoproteomic analysis of antibody response to cell wall-associated proteins of Candida tropicalis. J Appl Microbiol 117: 854-865. doi: 10.1111/jam.12562.
  • Leung AY, Chim CS, Ho PL, Cheng VC, Yuen KY, Lie AK, Au WY, Liang R, Kwong YL (2002) Candida tropicalis fungaemia in adult patients with haematological malignancies: clinical features and risk factors. J Hosp Infect 50: 316-319.
  • Long AT, Kenne E, Jung R, Fuchs TA, Renné T (2015) Contact system revisited: an interface between inflammation, coagulation, and innate immunity. J Thromb Haemost 14: 427-437. doi: 10.1111/jth.13235.
  • Ma CF, Li FQ, Shi LN, Hu YA, Wang Y, Huang M, Kong QQ (2013) Surveillance study of species distribution, antifungal susceptibility and mortality of nosocomial candidemia in a tertiary care hospital in China. BMC Infect Dis 13: 337. doi: 10.1186/1471-2334-13-337.
  • Magalhães YC, Bomfim MR, Melônio LC, Ribeiro PC, Cosme LM, Rhoden CR, Marques SG (2015) Clinical significance of the isolation of Candida species from hospitalized patients. Braz J Microbiol 46: 117-123. doi: 10.1590/S1517-838246120120296.
  • Mattsson E, Herwald H, Cramer H, Persson K, Sjobring U, Bjorck L (2001) Staphylococcus aureus induces release of bradykinin in human plasma. Infect Immun 69: 3877-3882.
  • McKay DG (1972) Participation of components of the blood coagulation system in the inflammatory response. Am J Pathol 67: 181-210.
  • Negri M, Silva S, Capoci IR, Azeredo J, Henriques M (2016) Candida tropicalis biofilms: biomass, metabolic activity and secreted aspartyl proteinase production. Mycopathologia 181: 217-224. doi: 10.1007/s11046-015-9964-4.
  • Negri M, Silva S, Henriques M, Oliveira R (2012) Insights into Candida tropicalis nosocomial infections and virulence factors. Eur J Clin Microbiol Infect Dis 31: 1399-1412.
  • Oehmcke S, Herwald H (2010) Contact system activation in severe infectious diseases. J Mol Med (Berl) 88: 121-126.
  • Okawa Y, Miyauchi M, Kobayashi H (2008) Comparison of pathogenicity of various Candida tropicalis strains. Biol Pharm Bull 31: 1507-1510.
  • Persson K, Mörgelin M, Lindbom L, Alm P, Björck L, Herwald H (2000) Severe lung lesions caused by Salmonella are prevented by inhibition of the contact system. J Exp Med 192: 1415-1424.
  • Pfaller MA, Diekema DJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20: 133-163.
  • Poltermann S, Kunert A, von der Heide M, Eck R, Hartmann A, Zipfel PF (2007) Gpm1p is a factor H, FHL-1-, and plasminogen-binding surface protein of Candida albicans. J Biol Chem 282: 37537-37544.
  • Priest SJ, Lorenz MC (2015) Characterization of Virulence-Related Phenotypes in Candida Species of the CUG Clade. Eukaryot Cell 14: 931-940. doi: 10.1128/EC.00062-15.
  • Rapala-Kozik M, Bras G, Chruscicka B, Karkowska-Kuleta J, Sroka A, Herwald H, Nguyen KA, Eick S, Potempa J, Kozik A (2011) Adsorption of components of the plasma kinin-forming system on the surface of Porphyromonas gingivalis involves gingipains as the major docking platforms. Infect Immun 79: 797-805. doi: 10.1128/IAI.00966-10.
  • Rapala-Kozik M, Karkowska J, Jacher A, Golda A, Barbasz A, Guevara-Lora I, Kozik A (2008) Kininogen adsorption to the cell surface of Candida spp. Int Immunopharmacol 8: 237-241. doi: 10.1016/j.intimp.2007.07.005.
  • Rapala-Kozik M, Karkowska-Kuleta J, Ryzanowska A, Golda A, Barbasz A, Faussner A, Kozik A (2010) Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp. Biol Chem 391: 823-830.
  • Sardi JC, Scorzoni L, Bernardi T, Fusco-Almeida AM, Mendes Giannini MJ (2013) Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options. J Med Microbiol 62: 10-24.
  • Sardi Jde C, Pitangui Nde S, Rodríguez-Arellanes G, Taylor ML, Fusco-Almeida AM, Mendes-Giannini MJ (2014) Highlights in pathogenic fungal biofilms. Rev Iberoam Micol 31: 22-29. doi: 10.1016/j.riam.2013.09.014.
  • Scicli AG, Mindroiu T, Scicli G, Carretero OA (1982) Blood kinins, their concentration in normal subjects and in patients with congenital deficiency in plasma prekallikrein and kininogen. J Lab Clin Med 100: 81-93.
  • Seweryn K, Karkowska-Kuleta J, Wolak N, Bochenska O, Kedracka-Krok S, Kozik A, Rapala-Kozik M (2015) Kinetic and thermodynamic characterization of the interactions between the components of human plasma kinin-forming system and isolated and purified cell wall proteins of Candida albicans. Acta Biochim Pol 62: 825-835. doi: 10.18388/abp.2015_1142.
  • Silva S, Negri M, Henriques M, Oliveira R, Williams DW, Azeredo J (2012) Candida glabrata, Candida parapsilosis and Candida tropicalis: biology, epidemiology, pathogenicity and antifungal resistance. FEMS Microbiol Rev 36: 288-305.
  • Tan TY, Hsu LY, Alejandria MM, Chaiwarith R, Chinniah T, Chayakulkeeree M et al. (2016) Antifungal susceptibility of invasive Candida bloodstream isolates from the Asia-Pacific region. Med Mycol 54: 471-477. doi: 10.1093/mmy/myv114.
  • Tapper H, Herwald H (2000) Modulation of hemostatic mechanisms in bacterial infectious diseases. Blood 96: 2329-2337.
  • Tronchin G, Pihet M, Lopes-Bezerra LM, Bouchara JP (2008) Adherence mechanisms in human pathogenic fungi. Med Mycol 46: 749-772. doi: 10.1080/13693780802206435.
  • White MF, Fothergill-Gilmore LA, Kelly SM, Price NC (1993) Dissociation of the tetrameric phosphoglycerate mutase from yeast by a mutation in the subunit contact region. Biochem J 295: 743-748.
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