Binding of human plasminogen and high-molecular-mass kininogen by cell surface-exposed proteins of Candida parapsilosis

Justyna Karkowska-Kuleta; Dorota Zajac; Grazyna Bras; Oliwia Bochenska; Maria Rapala-Kozik; Andrzej Kozik

doi:10.18388/abp.2017_1609

Justyna Karkowska-Kuleta Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland
Dorota Zajac Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland
Grazyna Bras Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland
Oliwia Bochenska Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland
Maria Rapala-Kozik Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland
Andrzej Kozik Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland

DOI: https://doi.org/10.18388/abp.2017_1609

Abstract

Pathogenic microbes can recruit to their cell surface human proteins that are components of important proteolytic cascades involved in coagulation, fibrinolysis and innate immune response. Once located at the bacterial or fungal surface such deployed proteins might be utilized by pathogens to facilitate invasion and dissemination within host organism by interfering with functionality of these systems or by exploiting specific activity of bound enzymes.

The aim of the present study was to characterize this phenomenon in Candida parapsilosis (Ashford) Langeron et Talice ― an important causative agent of systemic fungal infections (candidiases and candidemias) in humans. We investigated the interactions of fungal surface-exposed proteins with plasminogen (HPG) and high-molecular-mass kininogen (HK) ― the crucial components of human fibrinolytic system and proinflammatory/procoagulant contact-activated kinin-forming system, respectively.

After confirming an ability of fungal surface-exposed proteins to bind HPG and HK, four of them ― two agglutinin-like sequence (Als) proteins CPAR2_404780 and CPAR2_404800, a heat shock protein Ssa2 and a moonlighting protein 6-phosphogluconate dehydrogenase 1 ― were purified using ion-exchange chromatography, gel filtration and chromatofocusing. Then, their affinities to HPG and HK were characterized with surface plasmon resonance measurements. The determined dissociation constants for the investigated protein-protein complexes were within a 10^–7 M order for HPG binding and in a range of 10^–8-10^–9 M for HK binding.

Detailed characterization of adsorption of these two important plasma proteins on the fungal cell surface may help to increase our understanding of molecular mechanisms of C. parapsilosis-dependent candidiasis.

References

Benjamin DK Jr, Stoll BJ, Fanaroff AA, McDonald SA, Oh W et al. (2006) Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months. Pediatrics 117: 84-92.

Bertini A, Zoppo M, Lombardi L, Rizzato C, De Carolis E, Vella A, Torelli R, Sanguinetti M, Tavanti A (2016) Targeted gene disruption in Candida parapsilosis demonstrates a role for CPAR2_404800 in adhesion to a biotic surface and in a murine model of ascending urinary tract infection. Virulence 7: 85-97. http://doi.org/10.1080/21505594.2015.1112491.

Bhattacharya S, Ploplis VA, Castellino FJ (2012) Bacterial plasminogen receptors utilize host plasminogen system for effective invasion and dissemination. J Biomed Biotechnol 2012: 482096. http://doi.org/10.1155/2012/482096.

Bonassoli LA, Bertoli M, Svidzinski TI (2005) High frequency of Candida parapsilosis on the hands of healthy hosts. J Hosp Infect. 59: 159-162.

Bouchara JP, Tronchin G, Annaix V, Robert R, Senet JM. (1990) Laminin receptors on Candida albicans germ tubes. Infect Immun. 51: 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, Kamysz W, Kozik A (2013) Release of biologically active kinin peptides, Met-Lys-bradykinin and Leu-Met-Lys-bradykinin from human kininogens by two major secreted aspartic proteases of Candida parapsilosis. Peptides 48: 114-123. http://doi.org/10.1016/j.peptides.2013.08.003.

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. http://doi.org/10.1038/nature08064.

Castiblanco-Valencia MM, Fraga TR, Pagotto AH, Serrano SM, Abreu PA, Barbosa AS, Isaac L (2016) Plasmin cleaves fibrinogen and the human complement proteins C3b and C5 in the presence of Leptospira interrogans proteins: A new role of LigA and LigB in invasion and complement immune evasion. Immunobiology 221: 679-689. http://doi.org/10.1016/j.imbio.2016.01.001.

Chatzinikolaou I, Raad II (2000) Intravascular catheter-related infections: a preventable challenge in the critically ill. Semin Respir Infect 15: 264-271.

Chow BD, Linden JR, Bliss JM (2012) Candida parapsilosis and the neonate: epidemiology, virulence and host defense in a unique patient setting. Expert Rev Anti Infect Ther 10: 935-946. http://doi.org/10.1586/eri.12.74.

Crowe JD, Sievwright IK, Auld GC, Moore NR, Gow NA, Booth NA (2003) Candida albicans binds human plasminogen: identification of eight plasminogen-binding proteins. Mol Microbiol 47: 1637-1651.

Degen JL, Bugge TH, Goguen JD (2007) Fibrin and fibrinolysis in infection and host defense. J Thromb Haemost 5: 24-31.

Diekema DJ, Messer SA, Hollis RJ, Wenzel RP, Pfaller MA (1997) An outbreak of Candida parapsilosis prosthetic valve endocarditis. Diagn Microbiol Infect Dis 29: 147-153.

Duggan S, Leonhardt I, Hünniger K, Kurzai O (2015) Host response to Candida albicans bloodstream infection and sepsis. Virulence 6: 316-326. http://doi.org/10.4161/21505594.2014.988096.

Fathi N, Mohammadi R, Tabatabaiefar MA, Ghahri M, Sadrossadati SZ (2016) Sequence-identification of Candida species isolated from candidemia. Adv Biomed Res 5: 150. http://doi.org/10.4103/2277-9175.188485.

Frick IM, Björck L, Herwald H (2007) The dual role of the contact system in bacterial infectious disease. Thromb Haemost 98: 497-502.

Funk J, Schaarschmidt B, Slesiona S, Hallström T, Horn U, Brock M (2016) The glycolytic enzyme enolase represents a plasminogen-binding protein on the surface of a wide variety of medically important fungal species. Int J Med 306: 59-68. http://doi.org/10.1016/j.ijmm.2015.11.005.

Gacser A (2016) Adhesins in Candida parapsilosis: Understudied players in virulence. Virulence 7: 65-67. http://doi.org/10.1080/21505594.2015.1135288.

Garzoni C, Nobre VA, Garbino J (2007) Candida parapsilosis endocarditis: a comparative review of the literature. Eur J Clin Microbiol Infect Dis 26: 915-926.

Gogol M, Ostrowska D, Klaga K, Bochenska O, Wolak N, Aoki W, Ueda M, Kozik A, Rapala-Kozik M (2016) Inactivation of α1-proteinase inhibitor by Candida albicans aspartic proteases favors the epithelial and endothelial cell colonization in the presence of neutrophil extracellular traps. Acta Biochim Pol 63: 167-175. http://doi.org/10.18388/abp.2015_1163.

Herwald H, Mörgelin M, Dahlbäck B, Björck L (2003) Interactions between surface proteins of Streptococcus pyogenes and coagulation factors modulate clotting of human plasma. J Thromb Haemost 1: 284-291.

Holm K, Frick IM, Björck L, Rasmussen M (2011) Activation of the contact system at the surface of Fusobacterium necrophorum represents a possible virulence mechanism in Lemièrre's syndrome. Infect Immun 79: 3284-3290. http://doi.org/10.1128/IAI.05264-11.

Hoyer LL, Cota E (2016) Candida albicans Agglutinin-Like Sequence (Als) Family Vignettes: A Review of Als Protein Structure and Function. Front Microbiol 7: 280. http://doi.org/10.3389/fmicb.2016.00280.

Huish S, Thelwell C, Longstaff C (2017) Activity Regulation by Fibrinogen and Fibrin of Streptokinase from Streptococcus Pyogenes. PLoS One 12: e0170936. http://doi.org/10.1371/journal.pone.0170936.

Jacobi J (2002) Pathophysiology of sepsis. Am J Health Syst Pharm 59: S3-8.

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.

Juyal D, Sharma M, Pal S, Rathaur VK, Sharma N (2013) Emergence of non-albicans Candida species in neonatal candidemia. N Am J Med Sci 5: 541-545. http://doi.org/10.4103/1947-2714.118919.

Kapteyn JC, Montijn RC, Dijkgraaf GJ, Van den Ende H, Klis FM (1995) Covalent association of beta-1,3-glucan with beta-1,6-glucosylated mannoproteins in cell walls of Candida albicans. J Bacteriol 177: 3788-3792.

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 fungal cell wall and mapping the cell wall-binding regions on kininogen molecule. Peptides 32: 2488-2496. http://doi.org/10.1016/j.peptides.2011.10.021.

Karkowska-Kuleta J, Kozik A (2015) Cell wall proteome of pathogenic fungi. Acta Biochim Pol 62: 339-351. http://doi.org/10.18388/abp.2015_1032.

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. http://doi.org/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. http://doi.org/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. http://doi. org/10.18388/abp.2015_1140.

Karkowska-Kuleta J, Zajac D, Bras G, Bochenska O, Seweryn K, Kedracka-Krok S, Jankowska U, Rapala-Kozik M, Kozik A (2016) Characterization of the interactions between human high-molecular-mass kininogen and cell wall proteins of pathogenic yeasts Candida tropicalis. Acta Biochim Pol 63: 427-436. http://doi.org/10.18388/abp.2016_1353.

Klis FM, Sosinska GJ, de Groot PW, Brul S (2009) Covalently linked cell wall proteins of Candida albicans and their role in fitness and virulence. FEMS Yeast Res 9: 1013-1028. http://doi.org/10.1111/j.1567-1364.2009.00541.x.

Kozik A, Gogol M, Bochenska O, Karkowska-Kuleta J, Wolak N, Kamysz W, Aoki W, Ueda M, Faussner A, Rapala-Kozik M (2015a) Kinin release from human kininogen by 10 aspartic proteases produced by pathogenic yeast Candida albicans. BMC Microbiol 15: 60. http://doi.org/10.1186/s12866-015-0394-8.

Kozik A, Karkowska-Kuleta J, Zajac D, Bochenska O, Kedracka-Krok S, Jankowska U, Rapala-Kozik M (2015b) Fibronectin-, vitronectin- and laminin-binding proteins at the cell walls of Candida parapsilosis and Candida tropicalis pathogenic yeasts. BMC Microbiol 15: 197. http://doi.org/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.

Li XS, Reddy MS, Baev D, Edgerton M (2003) Candida albicans Ssa1/2p is the cell envelope binding protein for human salivary histatin 5. J Biol Chem 278: 28553-28561.

Long AT, Kenne E, Jung R, Fuchs TA, Renné T (2016) Contact system revisited: an interface between inflammation, coagulation, and innate immunity. J Thromb Haemost 14: 427-437. http://doi.org/10.1111/jth.13235.

Loof TG, Deicke C, Medina E (2014) The role of coagulation/fibrinolysis during Streptococcus pyogenes infection. Front Cell Infect Microbiol. 4: 128. http://doi.org/10.3389/fcimb.2014.00128.

López-Ribot JL, Alloush HM, Masten BJ, Chaffin WL (1996) Evidence for presence in the cell wall of Candida albicans of a protein related to the hsp70 family. Infect Immun 64: 3333-3340.

Lovero G, De Giglio O, Montagna O, Diella G, Divenuto F, Lopuzzo M, Rutigliano S, Laforgia N, Caggiano G, Montagna MT (2016) Epidemiology of candidemia in neonatal intensive care units: a persistent public health problem. Ann Ig 28: 282-287. http://doi.org/10.7416/ai.2016.2107.

Luo S, Hoffmann R, Skerka C, Zipfel PF (2013) Glycerol-3-phosphate dehydrogenase 2 is a novel factor H-, factor H-like protein 1-, and plasminogen-binding surface protein of Candida albicans. J Infect Dis 207: 594-603. http://doi.org/10.1093/infdis/jis718.

Luo S, Poltermann S, Kunert A, Rupp S, Zipfel PF (2009) Immune evasion of the human pathogenic yeast Candida albicans: Pra1 is a Factor H, FHL-1 and plasminogen binding surface protein. Mol Immunol 47: 541-550. http://doi.org/10.1016/j.molimm.2009.07.017.

Lupetti A, Tavanti A, Davini P, Ghelardi E, Corsini V, Merusi I, Boldrini A, Campa M, Senesi S (2002) Horizontal transmission of Candida parapsilosis candidemia in a neonatal intensive care unit. J Clin Microbiol 40: 2363-2369.

Maeda H, Yamamoto T (1996) Pathogenic mechanisms induced by microbial proteases in microbial infections. Biol Chem Hoppe Seyler 377: 217-226.

Marín E, Parra-Giraldo CM, Hernández-Haro C, Hernáez ML, Nombela C, Monteoliva L, Gil C (2015) Candida albicans Shaving to Profile Human Serum Proteins on Hyphal Surface. Front Microbiol 6: 1343. http://doi.org/10.3389/fmicb.2015.01343.

Ng K, Schorr C, Reboli AC, Zanotti S, Tsigrelis C (2015) Incidence and mortality of sepsis, severe sepsis, and septic shock in intensive care unit patients with candidemia. Infect Dis (Lond) 47: 584-587. http://doi.org/10.3109/23744235.2015.1028100.

Nickel KF, Renné T (2012) Crosstalk of the plasma contact system with bacteria. Thromb Res 130: S78-83. http://doi.org/10.1016/j.thromres.2012.08.284.

Núñez-Beltrán A, López-Romero E, Cuéllar-Cruz M (2017) Identification of proteins involved in the adhesion of Candida species to different medical devices. Microb Pathog 107: 293-303. http://doi.org/10.1016/j.micpath.2017.04.009.

Oehmcke S, Herwald H (2010) Contact system activation in severe infectious diseases. J Mol Med (Berl )88: 121-126.

Pammi M, Holland L, Butler G, Gacser A, Bliss JM (2013) Candida parapsilosis is a significant neonatal pathogen: a systematic review and meta-analysis. Pediatr Infect Dis J 32: e206-216. http://doi.org/10.1097/INF.0b013e3182863a1c.

Peetermans M, Vanassche T, Liesenborghs L, Lijnen RH, Verhamme P (2016) Bacterial pathogens activate plasminogen to breach tissue barriers and escape from innate immunity. Crit Rev Microbiol 42: 866-882. http://doi.org/10.3109/1040841X.2015.1080214.

Pfaller MA, Andes DR, Diekema DJ, Horn DL, Reboli AC, Rotstein C, Franks B, Azie NE (2014) Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2,496 patients: data from the Prospective Antifungal Therapy (PATH) registry 2004-2008. PLoS One 9: e101510. http://doi.org/10.1371/journal.pone.0101510.

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.

Pongrácz J, Benedek K, Juhász E, Iván M, Kristóf K (2016) In vitro biofilm production of Candida bloodstream isolates: any association with clinical characteristics? J Med Microbiol 65: 272-277. http://doi.org/10.1099/jmm.0.000207.

Potempa J, Banbula A, Travis J (2000) Role of bacterial proteinases in matrix destruction and modulation of host responses. Periodontol 2000 24: 153-192.

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. http://doi.org/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. http://doi.org/10.1016/j.intimp.2007.07.005.

Sabino R, Sampaio P, Carneiro C, Rosado L, Pais C (2011) Isolates from hospital environments are the most virulent of the Candida parapsilosis complex. BMC Microbiol 11: 180. http://doi.org/10.1186/1471-2180-11-180.

Sanchez V, Vazquez JA, Barth-Jones D, Dembry L, Sobel JD, Zervos MJ (1993) Nosocomial acquisition of Candida parapsilosis: an epidemiologic study. Am J Med 94: 577-582.

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. http://doi.org/10.18388/abp.2015_1142.

Shannon O, Herwald H, Oehmcke S (2013) Modulation of the coagulation system during severe streptococcal disease. Curr Top Microbiol Immunol. 368: 189-205. http://doi.org/10.1007/82_2012_283.

Smeesters PR, McMillan DJ, Sriprakash KS (2010) The streptococcal M protein: a highly versatile molecule. Trends Microbiol 18: 275-282. http://doi.org/10.1016/j.tim.2010.02.007.

Sun H (2006) The interaction between pathogens and the host coagulation system. Physiology (Bethesda) 21: 281-288. http://doi.org/10.1152/physiol.00059.2005

Sun JN, Li W, Jang WS, Nayyar N, Sutton MD, Edgerton M (2008) Uptake of the antifungal cationic peptide Histatin 5 by Candida albicans Ssa2p requires binding to non-conventional sites within the ATPase domain. Mol Microbiol 70: 1246-1260.

Trofa D, Gácser A, Nosanchuk JD (2008) Candida parapsilosis, an Emerging Fungal Pathogen. Clin Microbiol Rev 21: 606-625. http://doi.org/10.1128/CMR.00013-08

Vieira ML, Naudin C, Mörgelin M, Romero EC, Nascimento AL, Herwald H (2016) Modulation of Hemostatic and Inflammatory Responses by Leptospira Spp. PLoS Negl Trop Dis 10: e0004713. http://doi.org/10.1371/journal.pntd.0004713.

Wadile RG, Bhate VM (2015) Study of clinical spectrum and risk factors of neonatal candidemia. Indian J Pathol Microbiol 58: 472-474. http://doi.org/10.4103/0377-4929.168888.

Wollein Waldetoft K, Svensson L, Mörgelin M, Olin AI, Nitsche-Schmitz DP, Björck L, Frick IM (2012) Streptococcal surface proteins activate the contact system and control its antibacterial activity. J Biol Chem 287: 25010-25018. http://doi.org/10.1074/jbc.M112.373217.

Yang YL, Leaw SN, Wang AH, Chen HT, Cheng WT, Lo HJ (2011) Characterization of yeasts colonizing in healthy individuals. Med Mycol 49: 103-106. http://doi.org/10.3109/13693786.2010.487076.

Yılmaz Karadağ F, Ergen P, Aydın Ö, Doğru A, Tanıdır B, Vahaboğlu MH (2016) Evaluation of epidemiological characteristics and risk factors affecting mortality in patients with candidemia. Turk J Med Sci 46: 1724-1728. http://doi.org/10.3906/sag-1505-70.