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Interaction of Candida albicans with host cells: virulence factors, host defense, escape strategies, and the microbiota

Journal of Microbiology volume 54, pages 149–169 (2016)Cite this article

Abstract

The interaction between Candida albicans and its host cells is characterized by a complex interplay between the expression of fungal virulence factors, which results in adherence, invasion and cell damage, and the host immune system, which responds by secreting proinflammatory cytokines, activating antimicrobial activities and killing the fungal pathogen. In this review we describe this interplay by taking a closer look at how C. albicans pathogenicity is induced and executed, how the host responds in order to prevent and clear an infection, and which mechanisms C. albicans has evolved to bypass these immune responses to avoid clearance. Furthermore, we review studies that show how the presence of other microorganisms affects this interplay.

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References

  • Abiko, Y., Jinbu, Y. Noguchi, T., Nishimura, M., Kusano, K., Amaratunga, P., Shibata, T., and Kaku, T. 2002. Upregulation of human beta-defensin 2 peptide expression in oral lichen planus, leukoplakia and candidiasis. An immunohistochemical study. Pathol. Res. Pr. 198, 537–542.

    CAS  Article  Google Scholar 

  • Adam, B., Baillie, G.S., and Douglas, L.J. 2002. Mixed species biofilms of Candida albicans and Staphylococcus epidermidis. J. Med. Microbiol. 41, 344–349.

    Article  Google Scholar 

  • Akira, S., Uematsu, S., and Takeuchi, O. 2006. Pathogen recognition and innate immunity. Cell 124, 783–801.

    PubMed  CAS  Article  Google Scholar 

  • Akpan, A. and Morgan, R. 2002. Oral candidiasis. Postgr. Med. J. 78, 455–459.

    CAS  Article  Google Scholar 

  • Al-Fattani, M.A. and Douglas, L.J. 2006. Biofilm matrix of Candida albicans and Candida tropicalis: chemical composition and role in drug resistance. J. Med. Microbiol. 55, 999–1008.

    PubMed  CAS  Article  Google Scholar 

  • Antonio, M.A.D., Hawes, S.E., and Hillier, S.L. 1999. The identification of vaginal Lactobacillus species and the demographic and microbiologic characteristics of women colonized by these species. J. Infect. Dis. 180, 1950–1956.

    PubMed  CAS  Article  Google Scholar 

  • Baena-Monroy, T., Moreno-Maldonado, V., Franco-Martínez, F., Aldape-Barrios, B., Qindós, G., and Sánchez-Vargas, L. 2005. Candida albicans, Staphylococcus aureus and Streptococcus mutans colonization in patients wearing dental prosthesis. Med. Oral Patol. Oral Cir. Bucal. 10, 27–39.

    Google Scholar 

  • Bagg, J. and Silverwood, R.W. 1986. Coagglutination reactions between Candida albicans and oral bacteria. J. Med. Microbiol. 22, 165–169.

    PubMed  CAS  Article  Google Scholar 

  • Baillie, G.S. and Douglas, L.J. 1998. Effect of growth rate on resistance of Candida albicans biofilms to antifungal agents. Antimicrob. Agents Chemother. 42, 1900–1905.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Bamford, C.V., d’Mello, A., Nobbs, A.H., Dutton, L.C., Vickerman, M.M., and Jenkinson, H.F. 2009. Streptococcus gordonii modulates Candida albicans biofilm formation through intergeneric communication. Infect. Immun. 77, 3696–3704.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Bates, S., de la Rosa, J.M., MacCallum, D.M., Brown, A.J.P., Gow, N.A.R., and Odds, F.C. 2007. Candida albicans Iff11, a secreted protein required for cell wall structure and virulence. Infect. Immun. 75, 2922–2928.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Bauernfeind, A., Hörl, G., Jungwirth, R., Petermüller, C., Przyklenk, B., Weisslein-Pfister, C., Bertele, R.M., and Harms, K. 1987. Qualitative and quantitative microbiological analysis of sputa of 102 patients with cystic fibrosis. Infection 15, 270–277.

    PubMed  CAS  Article  Google Scholar 

  • Bellocchio, S., Montagnoli, C., Bozza, S., Gaziano, R., Rossi, G., Mambula, S.S., Vecchi, A., Mantovani, A., Levitz, S.M., and Romani, L. 2004. The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J. Immunol. 172, 3059–3069.

    PubMed  CAS  Article  Google Scholar 

  • Ben-Yaacov, R., Knoller, S., Caldwell, G.A., Becker, J.M., and Koltin, Y. 1994. Candida albicans gene encoding resistance to benomyl and methotrexate is a multidrug resistance gene. Antimicrob. Agents Chemother. 38, 648–652.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Berman, J. and Sudbery, P.E. 2002. Candida albicans: a molecular revolution built on lessons from budding yeast. Nat. Rev. Genet. 3, 918–930.

    PubMed  CAS  Article  Google Scholar 

  • Bink, A., Vandenbosch, D., Coenye, T., Nelis, H., Cammue, B.P.A., and Thevissen, K. 2011. Superoxide dismutases are involved in Candida albicans biofilm persistence against miconazole. Antimicrob. Agents Chemother. 55, 4033–4037.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Biswas, S., Van Dijck, P., and Datta, A. 2007. Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans. Microbiol. Mol. Biol. Rev. 71, 348–376.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Blankenship, J.R. and Mitchell, A.P. 2006. How to build a biofilm: a fungal perspective. Curr. Opin. Microbiol. 9, 588–594.

    PubMed  CAS  Article  Google Scholar 

  • Bokor-Bratic, M., Cankovic, M., and Dragnic, N. 2013. Unstimulated whole salivary flow rate and anxiolytics intake are independently associated with oral Candida infection in patients with oral lichen planus. Eur. J. Oral Sci. 121, 427–433.

    PubMed  Article  Google Scholar 

  • Brodsky, I.E. and Monack, D. 2009. NLR-mediated control of inflammasome assembly in the host response against bacterial pathogens. Semin. Immunol. 21, 199–207.

    PubMed  CAS  Article  Google Scholar 

  • Brown, G.D. 2006. Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat. Rev. Immunol. 6, 33–43.

    PubMed  CAS  Article  Google Scholar 

  • Buffo, J., Herman, M.A., and Soll, D.R. 1984. A characterization of pH regulated dimorphism in Candida albicans. Mycopathologia 30, 21–30.

    Article  Google Scholar 

  • Calabrese, D., Bille, J., and Sanglard, D. 2000. A novel multidrug efflux transporter gene of the major facilitator superfamily from Candida albicans FLU1) conferring resistance to fluconazole. Microbiol. 146, 2743–2754.

    CAS  Article  Google Scholar 

  • Calderone, R.A. and Clancy, C.J. 2012. Candida and Candidiasis, Second Edition. ASM Press. Washington, DC,USA.

    Google Scholar 

  • Cambi, A., Gijzen, K., de Vries, I.J.M., Torensma, R., Joosten, B., Adema, G.J., Netea, M.G., Kullberg, B.J., Romani, L., and Figdor, C.G. 2003. The C-type lectin DC-SIGN (CD209) is an antigenuptake receptor for Candida albicans on dendritic cells. Eur. J. Immunol. 33, 532–538.

    PubMed  CAS  Article  Google Scholar 

  • Cambi, A., Netea, M.G., Mora-Montes, H.M., Gow, N.A.R., Hato, S.V, Lowman, D.W., Kullberg, B.J., Torensma, R., Williams, D.L., and Figdor, C.G. 2008. Dendritic cell interaction with Candida albicans critically depends on N-linked mannan. J. Biol. Chem. 283, 20590–20599.

    Article  CAS  Google Scholar 

  • Carlson, E. 1983. Enhancement by Candida albicans of Staphylococcus aureus, Serratia marcescens, and Streptococcus faecalis in the establishment of infection in mice. Infect. Immun. 39, 193–197.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Carlson, E. and Johnson, G. 1985. Protection by Candida albicans of Staphylococcus aureus in the establishment of dual infection in mice. Infect. Immun. 50, 655–659.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Cassat, J.E., Lee, C.Y., and Smeltzer, M.S. 2007. Investigation of biofilm formation in clinical isolates of Staphylococcus aureus. Methods Mol. Biol. 391, 127–144.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Cassone, A. 2015. Vulvovaginal Candida albicans infections: pathogenesis, immunity and vaccine prospects. BJOG 122, 785–794.

    PubMed  CAS  Article  Google Scholar 

  • Chaffin, W.L. 2008. Candida albicans cell wall proteins. Microbiol. Mol. Biol. Rev. 72, 495–544.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Chandra, J., Kuhn, D.M., Mukherjee, P.K., Hoyer, L.L., McCormick, T., and Ghannoum, M.A. 2001. Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J. Bacteriol. 183, 5385–5394.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Chang, H.T., Tsai, P.W., Huang, H.H., Liu, Y.S., Chien, T.S., and Lan, C.Y. 2012. LL37 and hBD-3 elevate the β-1,3-exoglucanase activity of Candida albicans Xog1p, resulting in reduced fungal adhesion to plastic. Biochem. J. 441, 963–970.

    PubMed  CAS  Article  Google Scholar 

  • Chen, C.P., Posy, S., Ben-Shaul, A., Shapiro, L., and Honig, B.H. 2005. Specificity of cell-cell adhesion by classical cadherins: Critical role for low-affinity dimerization through β-strand swapping. Proc. Natl. Acad. Sci. USA. 102, 8531–8536.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Cheng, S.C., Joosten, L.A., Kullberg, B.J., and Netea, M.G. 2012. Interplay between Candida albicans and the mammalian innate host defense. Infect. Immun. 80, 1304–1313.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Cheng, S.C., van de Veerdonk, F.L., Lenardon, M., Stoffels, M., Plantinga, T., Smeekens, S., Rizzetto, L., Mukaremera, L., Preechasuth, K., Cavalieri, D., et al. 2011. The dectin-1/inflammasome pathway is responsible for the induction of protective T-helper 17 responses that discriminate between yeasts and hyphae of Candida albicans. J. Leukoc. Biol. 90, 357–366.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Cheng, S.C., van de Veerdonk, F., Smeekens, S., Joosten, L.A.B., van der Meer, J.W.M., Kullberg, B.J., and Netea, M.G. 2010. Candida albicans dampens host defense by downregulating IL-17 production. J. Immunol. 185, 2450–2457.

    PubMed  CAS  Article  Google Scholar 

  • Clemons, K. and Stevens, D. 2001. Overview of host defense mechanisms in systemic mycoses and the basis for immunotherapy. Semin. Respir. Infect. 16, 60–66.

    PubMed  CAS  Article  Google Scholar 

  • Colina, A.R., Aumont, F., Deslauriers, N., Belhumeur, P., and de Repentigny, L. 1996. Evidence for degradation of gastrointestinal mucin by Candida albicans secretory aspartyl proteinase. Infect. Immun. 64, 4514–4519.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Conti, H.R. and Gaffen, S.L. 2010. Host responses to Candida albicans: Th17 cells and mucosal candidiasis. Microbes Infect. 12, 518–527.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Costerton, J.W., Lewandowski, Z., Caldwell, D.E., Korber, D.R., and Lappin-Scott, H.M. 1995. Microbial biofilms. Annu. Rev. Microbiol. 49, 711–745.

    PubMed  CAS  Article  Google Scholar 

  • Cua, D.J. and Tato, C.M. 2010. Innate IL-17-producing cells: the sentinels of the immune system. Nat. Rev. Immunol 10, 479–489.

    PubMed  CAS  Article  Google Scholar 

  • Cugini, C., Calfee, M.W., Farrow, J.M., Morales, D.K., Pesci, E.C., and Hogan, D.A. 2007. Farnesol, a common sesquiterpene, inhibits PQS production in Pseudomonas aeruginosa. Mol. Microbiol. 65, 896–906.

    PubMed  CAS  Article  Google Scholar 

  • Dalle, F., Wächtler, B., L’Ollivier, C., Holland, G., Bannert, N., Wilson, D., Labruère, C., Bonnin, A., and Hube, B. 2010. Cellular interactions of Candida albicans with human oral epithelial cells and enterocytes. Cell. Microbiol. 12, 248–271.

    PubMed  CAS  Article  Google Scholar 

  • Davis-Hanna, A., Piispanen, A., Stateva, L., and Hogan, D. 2008. Farnesol and dodecanol effects on the Candida albicans Ras1- cAMP signalling pathway and the regulation of morphogenesis. Mol. Microbiol. 67, 47–62.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • De Luca, A., Zelante, T., D’Angelo, C., Zagarella, S., Fallarino, F., Spreca, A., Iannitti, R.G., Bonifazi, P., Renauld, J.C., Bistoni, F., et al. 2010. IL-22 defines a novel immune pathway of antifungal resistance. Mucosal Immunol. 3, 361–373.

    PubMed  Article  CAS  Google Scholar 

  • de Macedo, J.L.S. and Santos, J.B. 2005. Bacterial and fungal colonization of burn wounds. Memórias do Inst. Oswaldo Cruz 100, 535–539.

    Article  Google Scholar 

  • Dennerstein, G.J. and Ellis, D.H. 2001. Oestrogen, glycogen and vaginal candidiasis. Aust N Z J Obstet. Gynaecol. 41, 326–328.

    PubMed  CAS  Article  Google Scholar 

  • Doherty, G.J. and McMahon, H.T. 2009. Mechanisms of endocytosis. Annu. Rev. Biochem. 78, 857–902.

    PubMed  CAS  Article  Google Scholar 

  • Edgerton, M., Koshlukova, S.E., Lo, T.E., Chrzan, B.G., Straubinger, R.M., and Raj, P.A. 1998. Candidacidal activity of salivary histatins. J. Biol. Chem. 273, 20438–20447.

    PubMed  CAS  Article  Google Scholar 

  • Fanning, S. and Mitchell, A.P. 2012. Fungal biofilms. PLoS Pathog. 8, e1002585.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Fehrmann, C., Jurk, K., Bertling, A., Seidel, G., Fegeler, W., Kehrel, B.E., Peters, G., Becker, K., and Heilmann, C. 2013. Role for the fibrinogen-binding proteins coagulase and Efb in the Staphylococcus aureus–Candida interaction. Int. J. Med. Microbiol. 303, 230–238.

    PubMed  CAS  Article  Google Scholar 

  • Feller, L., Khammissa, R.A., Chandran, R., Altini, M., and Lemmer, J. 2014. Oral candidosis in relation to oral immunity. J. Oral Pathol. Med. 43, 563–569.

    PubMed  CAS  Article  Google Scholar 

  • Fernández-Arenas, E., Bleck, C.K.E., Nombela, C., Gil, C., Griffiths, G., and Diez-Orejas, R. 2009. Candida albicans actively modulates intracellular membrane trafficking in mouse macrophage phagosomes. Cell. Microbiol. 11, 560–589.

    PubMed  Article  CAS  Google Scholar 

  • Fidel, P.L. 2007. History and update on host defense against vaginal candidiasis. Am. J. Reprod. Immunol. 57, 2–12.

    PubMed  Article  Google Scholar 

  • Fling, M., Kopf, J., Tamarkin, A., Gorman, J., Smith, H., and Koltin, Y. 1991. Analysis of a Candida albicans gene that encodes a novel mechanism for resistance to benomyl and methotrexate. Mol. Gen. Genet. MGG 227, 318–329.

    PubMed  CAS  Article  Google Scholar 

  • Foxman, B., Muraglia, R., Dietz, J., Sobel, J., and Wagner, J. 2013. Prevalence of recurrent vulvovaginal candidiasis in 5 European countries and the United States: results from an internet panel survey. J. Low Genit. Tract. Dis. 17, 340–345.

    PubMed  Article  Google Scholar 

  • Frank, C.F. and Hostetter, M.K. 2007. Cleavage of E-cadherin: a mechanism for disruption of the intestinal epithelial barrier by Candida albicans. Transl. Res. 149, 211–222.

    PubMed  CAS  Article  Google Scholar 

  • Frohner, I.E., Bourgeois, C., Yatsyk, K., Majer, O., and Kuchler, K. 2009. Candida albicans cell surface superoxide dismutases degrade host-derived reactive oxygen species to escape innate immune surveillance. Mol. Microbiol. 71, 240–252.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Gácser, A., Stehr, F., Kröger, C., Kredics, L., Schäfer, W., and Nosanchuk, J.D. 2007. Lipase 8 affects the pathogenesis of Candida albicans. Infect. Immun. 75, 4710–4718.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  • Gantner, B.N., Simmons, R.M., and Underhill, D.M. 2005. Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J. 24, 1277–1286.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Garey, K.W., Rege, M., Pai, M.P., Mingo, D.E., Suda, K.J., Turpin, R.S., and Bearden, D.T. 2006. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multiinstitutional study. Clin. Infect. Dis. 77030, 25–31.

    Article  Google Scholar 

  • Gaur, N.K. and Klotz, S.A. 1997. Expression, cloning, and characterization of a Candida albicans gene, ALA1, that confers adherence properties upon Saccharomyces cerevisiae for extracellular matrix proteins. Infect. Immun. 65, 5289–5294.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Geiger, J., Wessels, D., Lockhart, S.R., and Soll, D.R. 2004. Release of a potent polymorphonuclear leukocyte chemoattractant is regulated by white-opaque switching in Candida albicans. Infect. Immun. 72, 667–677.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Ghannoum, M.A. 2000. Potential role of phospholipases in virulence and fungal pathogenesis. Clin. Microbiol. Rev. 13, 122–143.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Ghosh, S., Navarathna, D.H.M.L.P., Roberts, D.D., Cooper, J.T., Atkin, A.L., Petro, T.M., and Nickerson, K.W. 2009. Arginineinduced germ tube formation in Candida albicans is essential for escape from murine macrophage line RAW 264.7. Infect. Immun. 77, 1596–1605.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Gibson, J., Sood, A., and Hogan, D.A. 2009. Pseudomonas aeruginosa-Candida albicans interactions: localization and fungal toxicity of a phenazine derivative. Appl. Environ. Microbiol. 75, 504–513.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Gladiator, A., Wangler, N., Trautwein-Weidner, K., and Leibund-Gut-Landmann, S. 2013. Cutting edge: IL-17–secreting innate lymphoid cells are essential for host defense against fungal infection. J. Immunol. 190, 521–525.

    PubMed  CAS  Article  Google Scholar 

  • Götz, F., Bannerman, T., and Schleifer, K.H. 2006. The Genera Staphylococcus and Macrococcus. In Dworkin, M., Falkow, S., Rosenberg, E., Schleifer, K.H., and Stackebrandt, E. (eds.), The Prokaryotes SE-1, pp. 5–75. Springer, USA.

    Chapter  Google Scholar 

  • Gow, N. 1997. Germ tube growth of Candida albicans. Curr. Top. Med. Mycol. 8, 43–55.

    PubMed  CAS  Google Scholar 

  • Gow, N.A.R., Brown, A.J.P., and Odds, F.C. 2002. Fungal morphogenesis and host invasion. Curr. Opin. Microbiol. 5, 366–371.

    PubMed  CAS  Article  Google Scholar 

  • Gow, N.A. and Hube, B. 2012. Importance of the Candida albicans cell wall during commensalism and infection. Curr. Opin. Microbiol. 15, 406–412.

    PubMed  CAS  Article  Google Scholar 

  • Gow, N.A.R., Netea, M.G., Munro, C.A., Ferwerda, G., Bates, S., Mora-Montes, H.M., Walker, L., Jansen, T., Jacobs, L., Tsoni, V., et al. 2007. Immune recognition of Candida albicans β-glucan by dectin-1. J. Infect. Dis. 196, 1565–1571.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Gow, N., Perera, T., Sherwood-Higham, J., Gooday, G., Gregory, D., and Marshall, D. 1994. Investigation of touch-sensitive responses by hyphae of the human pathogenic fungus Candida albicans. Scanning Microsc. 8, 705–710.

    PubMed  CAS  Google Scholar 

  • Gow, N.A., van de Veerdonk, F.L., Brown, A.J., and Netea, M.G. 2012. Candida albicans morphogenesis and host defence: discriminating invasion from colonization. Nat. Rev. Microbiol. 10, 112–122.

    CAS  Google Scholar 

  • Green, D.R. 2011. Means to an End: Apoptosis and Other Cell Death Mechanisms. Cold Spring Harbor Laboratory Press.

    Google Scholar 

  • Grimaudo, N.J., Nesbitt, W.E., and Clark, W.B. 1996. Coaggregation of Candida albicans oral Actinomyces species. Oral Microbiol. Immunol. 11, 59–61.

    PubMed  CAS  Article  Google Scholar 

  • Gropp, K., Schild, L., Schindler, S., Hube, B., Zipfel, P.F., and Skerka, C. 2009. The yeast Candida albicans evades human complement attack by secretion of aspartic proteases. Mol. Immunol. 47, 465–475.

    PubMed  CAS  Article  Google Scholar 

  • Guery, B.P., Arendrup, M.C., Auzinger, G., Azoulay, E., Borges Sá, M., Johnson, E.M., Müller, E., Putensen, C., Rotstein, C., Sganga, G., et al. 2009. Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis. Intensive Care Med. 35, 55–62.

    PubMed  Article  Google Scholar 

  • Hajjeh, R.A., Sofair, A.N., Harrison, L.H., Lyon, G.M., Arthingtonskaggs, B.A., Mirza, S.A., Phelan, M., Morgan, J., Lee-yang, W., Ciblak, M.A., et al. 2004. Incidence of bloodstream infections due to candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J. Clin. Microbiol. 42, 1519–1527.

    PubMed Central  PubMed  Article  Google Scholar 

  • Harriott, M.M. and Noverr, M.C. 2009. Candida albicans and Staphylococcus aureus Form polymicrobial biofilms: effects on antimicrobial resistance. Antimicrob. Agents Chemother. 53, 3914–3922.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Hebecker, B., Naglik, J.R., Hube, B., and Jacobsen, I.D. 2014. Pathogenicity mechanisms and host response during oral Candida albicans infections. Expert. Rev. Anti. Infect. Ther. 12, 867–879.

    PubMed  CAS  Article  Google Scholar 

  • Helmerhorst, E.J., Troxler, R.F., and Oppenheim, F.G. 2001. The human salivary peptide histatin 5 exerts its antifungal activity through the formation of reactive oxygen species. Proc. Natl. Acad. Sci. USA 98, 14637–14642.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Hermann, C., Hermann, J., Munzel, U., and Rüchel, R. 1999. Bacterial flora accompanying Candida yeasts in clinical specimens. Mycoses 42, 619–627.

    PubMed  CAS  Article  Google Scholar 

  • Herre, J., Marshall, A.S.J., Caron, E., Edwards, A.D., Williams, D.L., Schweighoffer, E., Tybulewicz, V., Sousa, C.R.e, Gordon, S., and Brown, G.D. 2004. Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages. Blood 104, 4038–4045.

    PubMed  CAS  Article  Google Scholar 

  • Hibino, K., Samaranayake, L.P., Hägg, U., Wong, R.W.K., and Lee, W. 2009. The role of salivary factors in persistent oral carriage of Candida in humans. Arch. Oral Biol. 54, 678–683.

    PubMed  CAS  Article  Google Scholar 

  • Hickey, D., Patel, M., Fahey, J., and Wira, C. 2011. Innate and adaptive immunity at mucosal surfaces of the female reproductive tract: stratification and integration of immune protection against the transmission of sexually transmitted infections. J. Reprod. Immunol. 88, 185–194.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Hickey, D.K., Fahey, J.V., and Wira, C.R. 2013. Mouse estrous cycle regulation of vaginal versus uterine cytokines, chemokines, a-/β-defensins and TLRs. Innate Immun. 19, 121–131.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  • Hiller, E., Zavrel, M., Hauser, N., Sohn, K., Burger-Kentischer, A., Lemuth, K., and Rupp, S. 2011. Adaptation, adhesion and invasion during interaction of Candida albicans with the host–focus on the function of cell wall proteins. Int. J. Med. Microbiol. 301, 384–389.

    PubMed  CAS  Article  Google Scholar 

  • Hogan, D.A. and Kolter, R. 2002. Pseudomonas-Candida interactions: an ecological role for virulence factors. Science 296, 2229–2232.

    PubMed  CAS  Article  Google Scholar 

  • Hogan, D.A., Vik, Å., and Kolter, R. 2004. A Pseudomonas aeruginosa quorum-sensing molecule influences Candida albicans morphology. Mol. Microbiol. 54, 1212–1223.

    PubMed  CAS  Article  Google Scholar 

  • Hollmig, S.T., Ariizumi, K., and Cruz, P.D. 2009. Recognition of non-self-polysaccharides by C-type lectin receptors dectin-1 and dectin-2. Glycobiology 19, 568–575.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Holmes, A.R., McNab, R., and Jenkinson, H.F. 1996. Candida albicans binding to the oral bacterium Streptococcus gordonii involves multiple adhesin-receptor interactions. Infect. Immun. 64, 4680–4685.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Holmes, A.R., van der Wielen, P., Cannon, R.D., Ruske, D., and Dawes, P. 2006. Candida albicans binds to saliva proteins selectively adsorbed to silicone. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 102, 488–494.

    PubMed  Article  Google Scholar 

  • Hornby, J.M., Jensen, E.C., Lisec, A.D., Tasto, J.J., Jahnke, B., Shoemaker, R., Dussault, P., and Nickerson, K.W. 2001. Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol. Appl. Environ. Microbiol. 67, 2982–2992.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Hoyer, L.L. 2001. The ALS gene family of Candida albicans. Trends Microbiol. 9, 176–180.

    PubMed  CAS  Article  Google Scholar 

  • Hube, B., Stehr, F., Bossenz, M., Mazur, A., Kretschmar, M., and Schäfer, W. 2000. Secreted lipases of Candida albicans: cloning, characterisation and expression analysis of a new gene family with at least ten members. Arch. Microbiol. 174, 362–374.

    PubMed  CAS  Article  Google Scholar 

  • Hughes, W. and Kim, H. 1973. Mycoflora in cystic fibrosis: Some ecologic aspects of Pseudomonas aeruginosa and Candida albicans. Mycopathol. Mycol. Appl. 50, 261–269.

    PubMed  CAS  Article  Google Scholar 

  • Ibata-Ombetta, S., Idziorek, T., Trinel, P.A., Poulain, D., and Jouault, T. 2003. Candida albicans phospholipomannan promotes survival of phagocytosed yeasts through modulation of bad phosphorylation and macrophage apoptosis. J. Biol. Chem. 278, 13086–13093.

    PubMed  CAS  Article  Google Scholar 

  • Jacobsen, I.D., Wilson, D., Wächtler, B., Brunke, S., Naglik, J.R., and Hube, B. 2012. Candida albicans dimorphism as a therapeutic target. Expert. Rev. Anti. Infect. Ther. 10, 85–93.

    PubMed  Article  Google Scholar 

  • Jenkinson, H. and Douglas, L. 2002. Candida interactions with bacterial biofilms, pp. 357–373. In Brogden, K. and Guthmiller, J. (eds.), Polymicrobial Infections and Disease. ASM Press. Washington, DC, USA.

    Chapter  Google Scholar 

  • Jenkinson, H.F., Lala, H.C., and Shepherd, M.G. 1990. Coaggregation of Streptococcus sanguis and other streptococci with Candida albicans. Infect. Immun. 58, 1429–1436.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Joly, S., Ma, N., Sadler, J.J., Soll, D.R., Cassel, S.L., and Sutterwala, F.S. 2009. Candida albicans hyphae formation triggers activation of the Nlrp3 inflammasome. J. Immunol. 183, 3578–3581.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Kaksonen, M., Sun, Y., and Drubin, D.G. 2003. A pathway for association of receptors, adaptors, and actin during endocytic internalization. Cell 115, 475–487.

    PubMed  CAS  Article  Google Scholar 

  • Kaminishi, H., Miyaguchi, H., Tamaki, T., Suenaga, N., Hisamatsu, M., Mihashi, I., Matsumoto, H., Maeda, H., and Hagihara, Y. 1995. Degradation of humoral host defense by Candida albicans proteinase. Infect. Immun. 63, 984–988.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Kaneko, Y., Miyagawa, S., Takeda, O., Hakariya, M., Matsumoto, S., Ohno, H., and Miyazaki, Y. 2013. Real-time microscopic observation of candida biofilm development and effects due to micafungin and fluconazole. Antimicrob. Agents Chemother. 57, 2226–2230.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Káposzta, R., Tree, P., Maródi, L., and Gordon, S. 1998. Characteristics of invasive candidiasis in gamma interferon- and interleukin- 4-deficient mice: role of macrophages in host defense against Candida albicans. Infect. Immun. 66, 1708–1717.

    PubMed Central  PubMed  Google Scholar 

  • Kebaara, B.W., Langford, M.L., Navarathna, D.H.M.L.P., Dumitru, R., Nickerson, K.W., and Atkin, A.L. 2008. Candida albicans Tup1 is involved in farnesol-mediated inhibition of filamentous-growth induction. Eukaryot. Cell 7, 980–987.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Khader, S., Gaffen, S., and Kolls, J. 2009. Th17 cells at the crossroads of innate and adaptive immunity against infectious diseases at the mucosa. Mucosal Immunol. 2, 403–411.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Klein, R.S., Harris, C.A., Small, C.B., Moll, B., Lesser, M., and Friedland, G.H. 1984. Oral candidiasis in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome. N. Engl. J. Med. 311, 354–358.

    PubMed  CAS  Article  Google Scholar 

  • Kojic, E.M. and Darouiche, R.O. 2004. Candida infections of medical devices. Clin. Microbiol. Rev. 17, 255–267.

    PubMed Central  PubMed  Article  Google Scholar 

  • Koshlukova, S.E., Araujo, M.W.B., Baev, D., and Edgerton, M. 2000. Released ATP is an extracellular cytotoxic mediator in salivary histatin 5-induced killing of Candida albicans. Infect. Immun. 68, 6848–6856.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Krishnakumari, V., Rangaraj, N., and Nagaraj, R. 2009. Antifungal activities of human beta-defensins HBD-1 to HBD-3 and their C-terminal analogs Phd1 to Phd3. Antimicrob. Agents Chemother. 53, 256–260.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Kumagai, Y., Takeuchi, O., and Akira, S. 2015. Pathogen recognition by innate receptors. J. Infect. Chemother. 14, 86–92.

    Article  CAS  Google Scholar 

  • Kumamoto, C.A. and Vinces, M.D. 2005. Alternative Candida albicans lifestyles: growth on surfaces. Annu. Rev. Microbiol. 59, 113–133.

    PubMed  CAS  Article  Google Scholar 

  • Kumar, R., Chadha, S., Saraswat, D., Bajwa, J.S., Li, R.A., Conti, H.R., and Edgerton, M. 2011. Histatin 5 uptake by Candida albicans utilizes polyamine transporters Dur3 and Dur31 proteins. J. Biol. Chem. 286, 43748–43758.

    Google Scholar 

  • Kunze, D., Melzer, I., Bennett, D., Sanglard, D., MacCallum, D., Nörskau, J., Coleman, D.C., Odds, F.C., Schäfer, W., and Hube, B. 2005. Functional analysis of the phospholipase C gene CaPLC1 and two unusual phospholipase C genes, CaPLC2 and CaPLC3, of Candida albicans. Microbiology 151, 3381–3394.

    PubMed  CAS  Article  Google Scholar 

  • LaFleur, M.D., Kumamoto, C.A., and Lewis, K. 2006. Candida albicans biofilms produce antifungal-tolerant persister cells. Antimicrob. Agents Chemother. 50, 3839–3846.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Lamkanfi, M., Festjens, N., Declercq, W., Vanden Berghe, T., and Vandenabeele, P. 2006. Caspases in cell survival, proliferation and differentiation. Cell Death Differ. 14, 44–55.

    PubMed  Article  CAS  Google Scholar 

  • Leberer, E., Harcus, D., Broadbent, I., Clark, K., Dignard, D., Ziegelbauer, K., Schmidt, A., Gow, N., Brown, A., and Thomas, D. 1996. Signal transduction through homologs of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans. Proc. Natl. Acad. Sci. USA 93, 13217–13222.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Lehrer, R.I. and Ganz, T. 1999. Antimicrobial peptides in mammalian and insect host defence. Curr. Opin. Immunol. 11, 23–27.

    PubMed  CAS  Article  Google Scholar 

  • LeibundGut-Landmann, S., Grosz, O., Robinson, M.J., Osorio, F., Slack, E.C., Tsoni, S.V., Schweighoffer, E., Tybulewicz, V., Brown, G.D., Ruland, J., et al. 2007. Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat. Immunol. 8, 630–638.

    PubMed  CAS  Article  Google Scholar 

  • Leidich, S.D., Ibrahim, A.S., Fu, Y., Koul, A., Jessup, C., Vitullo, J., Fonzi, W., Mirbod, F., Nakashima, S., Nozawa, Y., et al. 1998. Cloning and disruption of caPLB1, a phospholipase B gene involved in the pathogenicity of Candida albicans. J. Biol. Chem. 273, 26078–26086.

    Article  Google Scholar 

  • Lermann, U. and Morschhäuser, J. 2008. Secreted aspartic proteases are not required for invasion of reconstituted human epithelia by Candida albicans. Microbiology 154, 3281–3295.

    PubMed  CAS  Article  Google Scholar 

  • Lewis, K. 2010. Persister cells. Annu. Rev. Microbiol. 64, 357–372.

    PubMed  CAS  Article  Google Scholar 

  • Li, M., Chen, Q., Tang, R., Shen, Y., and Liu, W. 2011. The expression of beta-defensin-2,3 and LL-37 induced by Candida albicans phospholipomannan in human keratinocytes. J. Dermatol. Sci. 61, 72–75.

    PubMed  CAS  Article  Google Scholar 

  • Li, R., Kumar, R., Tati, S., Puri, S., and Edgerton, M. 2013. Candida albicans Flu1-mediated efflux of salivary histatin 5 reduces its cytosolic concentration and fungicidal activity. Antimicrob. Agents Chemother. 57, 1832–1839.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Li, F. and Palecek, S.P. 2003. EAP1, a Candida albicans gene involved in binding human epithelial cells. Eukaryot. Cell 2, 1266–1273.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Li, F. and Palecek, S.P. 2008. Distinct domains of the Candida albicans adhesin Eap1p mediate cell-cell and cell-substrate interactions. Microbiology 154, 1193–1203.

    PubMed  CAS  Article  Google Scholar 

  • Liu, H., Kohler, J., and Fink, G.R. 1994. Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science 266, 1723–1726.

    PubMed  CAS  Article  Google Scholar 

  • Liu, L., Okada, S., Kong, X.F., Kreins, A.Y., Cypowyj, S., Abhyankar, A., Toubiana, J., Itan, Y., Audry, M., Nitschke, P., et al. 2011. Gainof-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J. Exp. Med. 208, 1635–1648.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Loza, L., Fu, Y., Ibrahim, A.S., Sheppard, D.C., Filler, S.G., and Edwards, J.E. 2004. Functional analysis of the Candida albicans ALS1 gene product. Yeast 21, 473–482.

    PubMed  CAS  Article  Google Scholar 

  • Luo, S., Blom, A.M., Rupp, S., Hipler, U.C., Hube, B., Skerka, C., and Zipfel, P.F. 2011. The pH-regulated antigen 1 of Candida albicans binds the human complement inhibitor C4b-binding protein and mediates fungal complement evasion. J. Biol. Chem. 286, 8021–8029.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Luo, S., Hartmann, A., Dahse, H.M., Skerka, C., and Zipfel, P.F. 2010. Secreted pH-regulated antigen 1 of Candida albicans blocks activation and conversion of complement C3. J. Immunol. 185, 2164–2173.

    PubMed  CAS  Article  Google Scholar 

  • Luo, S., Poltermann, S., Kunert, A., Rupp, S., and Zipfel, P.F. 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.

    PubMed  CAS  Article  Google Scholar 

  • Luo, S., Skerka, C., Kurzai, O., and Zipfel, P.F. 2013. Complement and innate immune evasion strategies of the human pathogenic fungus Candida albicans. Mol. Immunol. 56, 161–169.

    PubMed  CAS  Article  Google Scholar 

  • Marcil, A., Harcus, D., Thomas, D.Y., and Whiteway, M. 2002. Candida albicans killing by RAW 264.7 mouse macrophage cells: effects of candida genotype, infection ratios, and gamma interferon treatment. Infect. Immun. 70, 6319–6329.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Mardon, D., Balish, E., and Phillips, A. 1969. Control of dimorphism in a biochemical variant of Candida albicans. J. Bacteriol. 100, 701–707.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Marger, M.D. and Saier Jr., M.H. 1993. A major superfamily of transmembrane facilitators that catalyse uniport, symport and antiport. Trends Biochem. Sci. 18, 13–20.

    PubMed  CAS  Article  Google Scholar 

  • Maródi, L., Korchak, H.M., and Johnston, R.B. 1991. Mechanisms of host defense against Candida species. I. Phagocytosis by monocytes and monocyte-derived macrophages. J. Immunol. 146, 2783–2789.

    PubMed  Google Scholar 

  • Marr, K.A., Seidel, K., and White, T.C. 2000. Candidemia in allogeneic blood and marrow transplant recipients: evolution of risk factors after the adoption of prophylactic fluconazole. J. Infect. Dis. 181, 309–316.

    PubMed  CAS  Article  Google Scholar 

  • Martinon, F. and Tschopp, J. 2004. Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell 117, 561–574.

    PubMed  CAS  Article  Google Scholar 

  • Martinon, F., Mayor, A., and Tschopp, J. 2009. The inflammasomes: guardians of the body. Annu. Rev. Immunol. 27, 229–265.

    PubMed  CAS  Article  Google Scholar 

  • Mayer, F.L., Wilson, D., and Hube, B. 2013. Candida albicans pathogenicity mechanisms. Virulence 4, 119–128.

    PubMed Central  PubMed  Article  Google Scholar 

  • Mayer, F.L., Wilson, D., Jacobsen, I.D., Miramón, P., Groβe, K., and Hube, B. 2012. The novel Candida albicans transporter Dur31 is a multi-stage pathogenicity factor. PLoS Pathog. 8, e1002592.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • McCaig, L.F., McDonald, L.C., Mandal, S., and Jernigan, D.B. 2006. Staphylococcus aureus–associated skin and soft tissue infections in ambulatory care. Emerg. Infect. Dis. J. 12, 1715.

    Article  Google Scholar 

  • McGreal, E.P., Rosas, M., Brown, G.D., Zamze, S., Wong, S.Y.C., Gordon, S., Martinez-Pomares, L., and Taylor, P.R. 2006. The carbohydrate-recognition domain of Dectin-2 is a C-type lectin with specificity for high mannose. Glycobiol. 16, 422–430.

    CAS  Article  Google Scholar 

  • McKenzie, C.G.J., Koser, U., Lewis, L.E., Bain, J.M., Mora-Montes, H.M., Barker, R.N., Gow, N.A.R., and Erwig, L.P. 2010. Contribution of Candida albicans cell wall components to recognition by and escape from murine macrophages. Infect. Immun. 78, 1650–1658.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • McMahon, H.T. and Boucrot, E. 2011. Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nat. Rev. Mol. Cell Biol. 12, 517–533.

    PubMed  CAS  Article  Google Scholar 

  • Meiller, T.F., Hube, B., Schild, L., Shirtliff, M.E., Scheper, M.A., Winkler, R., Ton, A., and Jabra-Rizk, M.A. 2009. A novel immune evasion strategy of Candida albicans: Proteolytic cleavage of a salivary antimicrobial peptide. PLoS One 4, e5039.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  • Merrifield, C.J., Feldman, M.E., Wan, L., and Almers, W. 2002. Imaging actin and dynamin recruitment during invagination of single clathrin-coated pits. Nat. Cell Biol. 4, 691–698.

    PubMed  CAS  Article  Google Scholar 

  • Miceli, M.H., Díaz, J.A., and Lee, S.A. 2011. Emerging opportunistic yeast infections. Lancet Infect. Dis. 11, 142–151.

    PubMed  Article  Google Scholar 

  • Modrzewska, B. and Kurnatowski, P. 2015. Adherence of Candida sp. to host tissues and cells as one of its pathogenicity features. Ann. Parasitol. 61, 3–9.

    PubMed  Google Scholar 

  • Moore, K.W., O’Garra, A., Malefyt, R.W., Vieira, P., and Mosmann, T.R. 1993. Interleukin-10. Annu. Rev. Immunol. 11, 165–190.

    PubMed  CAS  Article  Google Scholar 

  • Morales, D.K., Jacobs, N.J., Rajamani, S., Krishnamurthy, M., Cubillos-Ruiz, J.R., and Hogan, D.a 2010. Antifungal mechanisms by which a novel Pseudomonas aeruginosa phenazine toxin kills Candida albicans in biofilms. Mol. Microbiol. 78, 1379–1392.

    PubMed  CAS  Article  Google Scholar 

  • Moreno-Ruiz, E., Galán-Díez, M., Zhu, W., Fernández-Ruiz, E., D’Enfert, C., Filler, S.G., Cossart, P., and Veiga, E. 2009. Candida albicans internalization by host cells is mediated by a clathrindependent mechanism. Cell. Microbiol. 11, 1179–1189.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Moyes, D.L., Murciano, C., Runglall, M., Islam, A., Thavaraj, S., and Naglik, J.R. 2011. Candida albicans yeast and hyphae are discriminated by MAPK signaling in vaginal epithelial cells. PLoS One 6, e26580.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Moyes, D.L., Murciano, C., Runglall, M., Kohli, A., Islam, A., and Naglik, J.R. 2012. Activation of MAPK/c-Fos induced responses in oral epithelial cells is specific to Candida albicans and Candida dubliniensis hyphae. Med. Microbiol. Immunol. 201, 93–101.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Moyes, D.L., Richardson, J.P., and Naglik, J.R. 2015. Candida albicans-epithelial interactions and pathogenicity mechanisms: scratching the surface. Virulence 6, 338–346.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Moyes, D.L., Runglall, M., Murciano, C., Shen, C., Nayar, D., Thavaraj, S., Kohli, A., Islam, A., Mora-Montes, H., Challacombe, S.J., et al. 2010. A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells. Cell Host Microbe 8, 225–235.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Moyes, D.L., Shen, C., Murciano, C., Runglall, M., Richardson, J.P., Arno, M., Aldecoa-Otalora, E., and Naglik, J.R. 2014. Protection against epithelial damage during Candida albicans infection is mediated by PI3K/Akt and mammalian target of rapamycin signaling. J. Infect. Dis. 209, 1816–1826.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Naglik, J.R. and Moyes, D. 2011. Epithelial cell innate response to Candida albicans. Adv. Dent. Res. 23, 50–55.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Naglik, J.R., Moyes, D., Makwana, J., Kanzaria, P., Tsichlaki, E., Weindl, G., Tappuni, A.R., Rodgers, C.a., Woodman, A.J., Challacombe, S.J., et al. 2008. Quantitative expression of the Candida albicans secreted aspartyl proteinase gene family in human oral and vaginal candidiasis. Microbiology 154, 3266–3280.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Naglik, J.R., Moyes, D.L., Wächtler, B., and Hube, B. 2011. Candida albicans interactions with epithelial cells and mucosal immunity. Microbes Infect. 13, 963–976.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Nair, N., Biswas, R., Götz, F., and Biswas, L. 2014. Impact of Staphylococcus aureus on pathogenesis in polymicrobial infections. Infect. Immun. 82, 2162–2169.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  • Netea, M.G., Brown, G.D., Kullberg, B.J., and Gow, N.A.R. 2008. An integrated model of the recognition of Candida albicans by the innate immune system. Nat. Rev. Microbiol. 6, 67–78.

    PubMed  CAS  Article  Google Scholar 

  • Netea, M.G. and Maródi, L. 2010. Innate immune mechanisms for recognition and uptake of Candida species. Trends Immunol. 31, 346–353.

    PubMed  CAS  Article  Google Scholar 

  • Netea, M.G., Sutmuller, R., Hermann, C., Van der Graaf, C.A.A., Van der Meer, J.W.M., van Krieken, J.H., Hartung, T., Adema, G., and Kullberg, B.J. 2004. Toll-Like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells. J. Immunol. 172, 3712–3718.

    PubMed  CAS  Article  Google Scholar 

  • Nett, J.E., Crawford, K., Marchillo, K., and Andes, D.R. 2010. Role of Fks1p and matrix glucan in Candida albicans biofilm resistance to an echinocandin, pyrimidine, and polyene. Antimicrob. Agents Chemother. 54, 3505–3508.

    CAS  Article  Google Scholar 

  • Nett, J.E., Lepak, A.J., Marchillo, K., and Andes, D.R. 2009. Time course global gene expression analysis of an in vivo Candida biofilm. J. Infect. Dis. 200, 307–313.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Nett, J., Lincoln, L., Marchillo, K., Massey, R., Holoyda, K., Hoff, B., VanHandel, M., and Andes, D. 2007. Putative role of β-1,3 glucans in Candida albicans biofilm resistance. Antimicrob. Agents Chemother. 51, 510–520.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Niewerth, M. and Korting, H.C. 2001. Phospholipases of Candida albicans. Mycoses 44, 361–367.

    PubMed  CAS  Article  Google Scholar 

  • Nobile, C.J., Fox, E.P., Nett, J.E., Sorrells, T.R., Mitrovich, Q.M., Hernday, A.D., Tuch, B.B., Andes, D.R., and Johnson, A.D. 2012. A recently evolved transcriptional network controls biofilm development in Candida albicans. Cell 148, 126–138.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Nobile, C.J., Schneider, H.A., Nett, J.E., Sheppard, D.C., Filler, S.G., Andes, D.R., and Mitchell, A.P. 2008. Complementary adhesin function in C. albicans biofilm formation. Curr. Biol. 18, 1017–1024.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Noverr, M.C. and Huffnagle, G.B. 2004. Regulation of Candida albicans morphogenesis by fatty acid metabolites. Infect. Immun. 72, 6206–6210.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Odds, F.C. 1988. Candida and Candidosis. Baillière Tindall.

    Google Scholar 

  • Odds, F.C. 2008. Secreted proteinases and Candida albicans virulence. Microbiology 154, 3245–3246.

    PubMed  CAS  Article  Google Scholar 

  • Oever, J.T. and Netea, M.G. 2014. The bacteriome-mycobiome interaction and antifungal host defense. Eur. J. Immunol. 44, 3182–3191.

    PubMed  Article  CAS  Google Scholar 

  • Onishi, R.M. and Gaffen, S.L. 2010. Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease. Immunology 129, 311–321.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Otte, J.M., Zdebik, A.E., Brand, S., Chromik, A.M., Strauss, S., Schmitz, F., Steinstraesser, L., and Schmidt, W.E. 2009. Effects of the cathelicidin LL-37 on intestinal epithelial barrier integrity. Regul. Pept. 156, 104–117.

    PubMed  CAS  Article  Google Scholar 

  • Park, H., Myers, C.L., Sheppard, D.C., Phan, Q.T., Sanchez, A.A., E. Edwards, J., and Filler, S.G. 2005. Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis. Cell. Microbiol. 7, 499–510.

    PubMed  CAS  Article  Google Scholar 

  • Peleg, A.Y., Tampakakis, E., Fuchs, B.B., Eliopoulos, G.M., Moellering, R.C., and Mylonakis, E. 2008. Prokaryote-eukaryote interactions identified by using Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 105, 14585–14590.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Perlroth, J., Choi, B., and Spellberg, B. 2007. Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med. Mycol. 45, 321–346.

    PubMed  Article  Google Scholar 

  • Peschel, A. and Sahl, H.G. 2006. The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat. Rev. Microbiol. 4, 529–536.

    PubMed  CAS  Article  Google Scholar 

  • Peters, B.M., Ovchinnikova, E.S., Krom, B.P., Schlecht, L.M., Zhou, H., Hoyer, L.L., Busscher, H.J., van der Mei, H.C., Jabra-Rizk, M.A., and Shirtliff, M.E. 2012. Staphylococcus aureus adherence to Candida albicans hyphae is mediated by the hyphal adhesin Als3p. Microbiology 158, 2975–2986.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Pfaller, M.A. and Diekema, D.J. 2010. Epidemiology of invasive mycoses in North America. Crit. Rev. Microbiol. 36, 1–53.

    PubMed  Article  Google Scholar 

  • Phan, Q.T., Belanger, P.H., and Filler, S.G. 2000. Role of hyphal formation in interactions of Candida albicans with endothelial cells. Infect. Immun. 68, 3485–3490.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Phan, Q.T., Fratti, R.A., Prasadarao, N.V., Edwards, J.E., and Filler, S.G. 2005. N-cadherin mediates endocytosis of Candida albicans by endothelial cells. J. Biol. Chem. 280, 10455–10461.

    Article  CAS  Google Scholar 

  • Phan, Q.T., Myers, C.L., Fu, Y., Sheppard, D.C., Yeaman, M.R., Welch, W.H., Ibrahim, A.S., Edwards, J.E., and Filler, S.G. 2007. Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells. PLoS Biol. 5, e64.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  • Powell, B.L., Frey, C.L., and Drutz, D.J. 1984. Identification of a 17p-estradiol binding protein in Candida albicans and Candida (Torulopsis) glabrata. Exp. Mycol. 8, 304–313.

    CAS  Article  Google Scholar 

  • Prasad, R., De Wergifosse, P., Goffeau, A., and Balzi, E. 1995. Molecular cloning and characterization of a novel gene of Candida albicans, CDR1, conferring multiple resistance to drugs and antifungals. Curr. Genet. 27, 320–329.

    PubMed  CAS  Article  Google Scholar 

  • Puel, A., Cypowyj, S., Bustamante, J., Wright, J.F., Liu, L., Lim, H.K., Migaud, M., Israel, L., Chrabieh, M., Audry, M., et al. 2011. Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 332, 65–68.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Puel, A., Döffinger, R., Natividad, A., Chrabieh, M., Barcenas-Morales, G., Picard, C., Cobat, A., Ouachée-Chardin, M., Toulon, A., Bustamante, J., et al. 2010. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J. Exp. Med. 207, 291–297.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Puri, S., Kumar, R., Chadha, S., Tati, S., Conti, H.R., Hube, B., Cullen, P.J., and Edgerton, M. 2012. Secreted aspartic protease cleavage of Candida albicans Msb2 activates Cek1 MAPK signaling affecting biofilm formation and oropharyngeal candidiasis. PLoS One 7, e46020.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Ramage, G., Bachmann, S., Patterson, T.F., Wickes, B.L., and López-Ribot, J.L. 2002. Investigation of multidrug efflux pumps in relation to fluconazole resistance in Candida albicans biofilms. J. Antimicrob. Chemother. 49, 973–980.

    PubMed  CAS  Article  Google Scholar 

  • Ramage, G., Martínez, J.P., and López-Ribot, J.L. 2006. Candida biofilms on implanted biomaterials: a clinically significant problem. FEMS Yeast Res. 6, 979–986.

    PubMed  CAS  Article  Google Scholar 

  • Ramage, G., Mowat, E., Jones, B., Williams, C., and Lopez-Ribot, J. 2009. Our current understanding of fungal biofilms. Crit. Rev. Microbiol. 35, 340–355.

    PubMed  CAS  Article  Google Scholar 

  • Rauceo, J.M., De Armond, R., Otoo, H., Kahn, P.C., Klotz, S.A., Gaur, N.K., and Lipke, P.N. 2006. Threonine-rich repeats increase fibronectin binding in the Candida albicans adhesin Als5p. Eukaryot. Cell 5, 1664–1673.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Ray, T.L. and Payne, C.D. 1988. Scanning electron microscopy of epidermal adherence and cavitation in murine candidiasis: a role for Candida acid proteinase. Infect. Immun. 56, 1942–1949.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Re, F. and Strominger, J.L. 2001. Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells. J. Biol. Chem. 276, 37692–37699.

    PubMed  CAS  Article  Google Scholar 

  • Rollenhagen, C., Wöllert, T., Langford, G.M., and Sundstrom, P. 2009. Stimulation of cell motility and expression of late markers of differentiation in human oral keratinocytes by Candida albicans. Cell. Microbiol. 11, 946–966.

    PubMed  CAS  Article  Google Scholar 

  • Rosentul, D.C., Plantinga, T.S., Oosting, M., Scott, W.K., Velez Edwards, D.R., Smith, P.B., Alexander, B.D., Yang, J.C., Laird, G.M., Joosten, L.A.B., et al. 2011. Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia. J. Infect. Dis. 204, 1138–1145.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Rotstein, D., Parodo, J., Taneja, R., and Marshall, J.C. 2000. Phagocytosis of Candida albicans induces apoptosis of human neutrophils. Shock 14, 278–283.

    PubMed  CAS  Article  Google Scholar 

  • Saijo, S., Ikeda, S., Yamabe, K., Kakuta, S., Ishigame, H., Akitsu, A., Fujikado, N., Kusaka, T., Kubo, S., Chung, S., et al. 2010. Dectin-2 recognition of a-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity 32, 681–691.

    PubMed  CAS  Article  Google Scholar 

  • Sallusto, F. and Lanzavecchia, A. 2002. The instructive role of dendritic cells on T-cell responses. Arthritis Res. 4 Suppl 3, 127–1

    Article  Google Scholar 

  • Sandini, S., La Valle, R., De Bernardis, F., Macrì, C., and Cassone, A. 2007. The 65 kDa mannoprotein gene of Candida albicans encodes a putative β-glucanase adhesin required for hyphal morphogenesis and experimental pathogenicity. Cell. Microbiol. 9, 1223–1238.

    PubMed  CAS  Article  Google Scholar 

  • Sanglard, D. 2002. Resistance of human fungal pathogens to antifungal drugs. Curr. Opin. Microbiol. 5, 379–385.

    PubMed  CAS  Article  Google Scholar 

  • Sanglard, D., Ischer, F., Monod, M., and Bille, J. 1997. Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene. Microbiology 143, 405–416.

    PubMed  CAS  Article  Google Scholar 

  • Sasse, C., Hasenberg, M., Weyler, M., Gunzer, M., and Morschhäuser, J. 2013. White-opaque switching of Candida albicans allows immune evasion in an environment-dependent fashion. Eukaryot. Cell 12, 50–58.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Saville, S.P., Lazzell, A.L., Monteagudo, C., and Lopez-ribot, J.L. 2003. Engineered control of cell morphology in vivo reveals distinct roles for yeast and filamentous forms of Candida albicans during infection. Eukaryot. Cell 2, 1053–1060.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Schaller, M., Mailhammer, R., Grassl, G., Sander, C.A., Hube, B., and Korting, H.C. 2002. Infection of human oral epithelia with Candida species induces cytokine expression correlated to the degree of virulence. J. Invest. Dermatol. 118, 652–657.

    PubMed  CAS  Article  Google Scholar 

  • Schaller, M., Borelli, C., Korting, H.C., and Hube, B. 2005. Hydrolytic enzymes as virulence factors of Candida albicans. Mycoses 48, 365–377.

    PubMed  CAS  Article  Google Scholar 

  • Schauber, J., Svanholm, C., Termén, S., Iffland, K., Menzel, T., Scheppach, W., Melcher, R., Agerberth, B., Lührs, H., and Gudmundsson, G.H. 2003. Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways. Gut 52, 735–741.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Scherwitz, C. 1982. Ultrastructure of human cutaneous candidosis. J. Investig. Dermatol. 78, 200–205.

    PubMed  CAS  Article  Google Scholar 

  • Sealy, P.I., Garner, B., Swiatlo, E., Chapman, S.W., and Cleary, J.D. 2008. The interaction of mannose binding lectin (MBL) with mannose containing glycopeptides and the resultant potential impact on invasive fungal infection. Med. Mycol. 46, 531–539.

    PubMed  CAS  Article  Google Scholar 

  • Seider, K., Heyken, A., Lüttich, A., Miramón, P., and Hube, B. 2010. Interaction of pathogenic yeasts with phagocytes: survival, persistence and escape. Curr. Opin. Microbiol. 13, 392–400.

    PubMed  CAS  Article  Google Scholar 

  • Sheppard, D.C., Yeaman, M.R., Welch, W.H., Phan, Q.T., Fu, Y., Ibrahim, A.S., Filler, S.G., Zhang, M., Waring, A.J., and Edwards, J.E. 2004. Functional and structural diversity in the Als protein family of Candida albicans. J. Biol. Chem. 279, 30480–30489.

    PubMed  CAS  Article  Google Scholar 

  • Shirtliff, M.E., Peters, B.M., and Jabra-Rizk, M.A. 2009. Cross-kingdom interactions: Candida albicans and bacteria. FEMS Microbiol. Lett. 299, 1–8.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Simonetti, N., Strippoli, V., and Cassone, A. 1974. Yeast-mycelial conversion induced by N-acetyl-D-glucosamine in Candida albicans. Nature 250, 344–346.

    PubMed  CAS  Article  Google Scholar 

  • Smeekens, S.P., Plantinga, T.S., van de Veerdonk, F.L., Heinhuis, B., Hoischen, A., Joosten, L.A., Arkwright, P.D., Gennery, A., Kullberg, B.J., Veltman, J.A., et al. 2011. STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis. PLoS One 6, e29248.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Sobel, J.D. 1992. Pathogenesis and treatment of recurrent vulvovaginal candidiasis. Clin. Infect. Dis. 14, S148–153.

    PubMed  Article  Google Scholar 

  • Sobel, J.D. 2015. Recurrent vulvovaginal candidiasis. Am. J. Obstet. Gynecol. DOI: http://dx.doi.org/10.1016/j.ajog.2015.06.067

    Google Scholar 

  • Spellberg, B. 2008. Novel insights into disseminated candidiasis: pathogenesis research and clinical experience converge. PLoS Pathog. 4, e38.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  • Staab, J.F., Bahn, Y.S., Tai, C.H., Cook, P.F., and Sundstrom, P. 2004. Expression of transglutaminase substrate activity on Candida albicans germ tubes through a coiled, disulfide-bonded N-terminal domain of Hwp1 requires C-terminal glycosylphosphatidylinositol modification. J. Biol. Chem. 279, 40737–40747.

    Article  CAS  Google Scholar 

  • Staab, J.F., Bradway, S.D., Fidel, P.L., and Sundstrom, P. 1999. Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1. Sciences 283, 1535–1538.

    CAS  Article  Google Scholar 

  • Stoldt, V.R., Sonneborn, A., Leuker, C.E., and Ernst, J.F. 1996. Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi. EMBO J. 16, 1982–1991.

    Article  Google Scholar 

  • Strober, W. 2004. Epithelial cells pay a Toll for protection. Nat. Med. 10, 898–900.

    PubMed  CAS  Article  Google Scholar 

  • Sudbery, P.E. 2011. Growth of Candida albicans hyphae. Nat. Rev. Microbiol. 9, 737–748.

    PubMed  CAS  Article  Google Scholar 

  • Sullivan, J.M.O., Jenkinson, H.F., and Cannon, R.D. 2000. Adhesion of Candida albicans to oral streptococci is promoted by selective adsorption of salivary proteins to the streptococcal cell surface. Microbiology 146, 41–48.

    Article  Google Scholar 

  • Sun, J.N., Li, W., Jang, W.S., Nayyar, N., Sutton, M.D., and 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.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Sun, J.N., Solis, N.V., Phan, Q.T., Bajwa, J.S., Kashleva, H., Thompson, A., Liu, Y., Dongari-Bagtzoglou, A., Edgerton, M., and Filler, S.G. 2010. Host cell invasion and virulence mediated by Candida albicans Ssa1. PLoS Pathog. 6, e1001181.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  • Sundstrom, P., Balish, E., and Allen, C.M. 2002. Essential role of the Candida albicans transglutaminase substrate, hyphal wall protein 1, in lethal oroesophageal candidiasis in immunodeficient mice. J. Infect. Dis. 185, 521–530.

    PubMed  CAS  Article  Google Scholar 

  • Swidergall, M. and Ernst, J.F. 2014. Interplay between Candida albicans and the antimicrobial peptide armory. Eukaryot. Cell 13, 950–957.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  • Swidergall, M., Ernst, A.M., and Ernst, J.F. 2013. Candida albicans mucin Msb2 is a broad-range protectant against antimicrobial peptides. Antimicrob. Agents Chemother. 57, 3917–3922.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Szafranski-Schneider, E., Swidergall, M., Cottier, F., Tielker, D., Román, E., Pla, J., and Ernst, J.F. 2012. Msb2 shedding protects Candida albicans against antimicrobial peptides. PLoS Pathog. 8, e1002501.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Taff, H.T., Nett, J.E., Zarnowski, R., Ross, K.M., Sanchez, H., Cain, M.T., Hamaker, J., Mitchell, A.P., and Andes, D.R. 2012. A Candida biofilm-induced pathway for matrix glucan delivery: implications for drug resistance. PLoS Pathog. 8, e1002848.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Takesue, Y., Kakehashi, M., Ohge, H., Imamura, Y., Murakami, Y., Sasaki, M., Morifuji, M., Yokoyama, Y., Kouyama, M., Yokoyama, T., et al. 2004. Combined assessment of beta-D-glucan and degree of Candida colonization before starting empiric therapy for candidiasis in surgical patients. World J. Surg. 28, 625–630.

    PubMed  Article  Google Scholar 

  • Takezaki, S., Yamada, M., Kato, M., Park, M.J., Maruyama, K., Yamazaki, Y., Chida, N., Ohara, O., Kobayashi, I., and Ariga, T. 2012. Chronic mucocutaneous candidiasis caused by a gain-of-function mutation in the STAT1 DNA-binding domain. J. Immunol. 189, 1521–1526.

    PubMed  CAS  Article  Google Scholar 

  • Taschdjian, C., Burchall, J., and Kozinn, P. 1960. Rapid identification of Candida albicans by filamentation on serum and serum substitutes. AMA. J. Dis. Child. 99, 212–215.

    PubMed  CAS  Google Scholar 

  • Tsai, P.W., Yang, C.Y., Chang, H.T., and Lan, C.Y. 2011. Human antimicrobial peptide LL-37 inhibits adhesion of Candida albicans by interacting with yeast cell-wall carbohydrates. PLoS One 6, e17755.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Underhill, D.M. and Iliev, I.D. 2014. The mycobiota: interactions between commensal fungi and the host immune system. Nat. Rev. Immunol. 14, 405–416.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Uppuluri, P., Chaturvedi, A.K., Srinivasan, A., Banerjee, M., Ramasubramaniam, A.K., Köhler, J.R., Kadosh, D., and Lopez-Ribot, J.L. 2010. Dispersion as an important step in the Candida albicans biofilm developmental cycle. PLoS Pathog. 6, e1000828.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  • Urban, C.F., Reichard, U., Brinkmann, V., and Zychlinsky, A. 2006. Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell. Microbiol. 8, 668–676.

    PubMed  CAS  Article  Google Scholar 

  • Urban, C.F., Ermert, D., Schmid, M., Abu-Abed, U., Goosmann, C., Nacken, W., Brinkmann, V., Jungblut, P.R., and Zychlinsky, A. 2009. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog. 5, e1000639.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  • Van’t Wout, J.W., Linde, I., Leijh, P.C.J., and van Furth, R. 1988. Contribution of granulocytes and monocytes to resistance against experimental disseminated Candida albicans infection. Eur. J. Clin. Microbiol. Infect. Dis. 7, 736–741.

    Article  Google Scholar 

  • Van de Veerdonk, F.L. and Joosten, L.A.B. 2015. The interplay between inflammasome activation and antifungal host defense. Immunol. Rev. 265, 172–180.

    PubMed  Article  CAS  Google Scholar 

  • Van de Veerdonk, F.L., Kullberg, B.J., and Netea, M.G. 2010. Pathogenesis of invasive candidiasis. Curr. Opin. Crit. Care 16, 453–459.

    PubMed  Article  Google Scholar 

  • Van de Veerdonk, F.L., Plantinga, T., Hoischen, A., Smeekens, S., Joosten, L., Gilissen, C., Arts, P., Rosentul, D., Carmichael, A., Smits-van der Graaf, C., et al. 2011. STAT1 Mutations in autosomal dominant chronic mucocutaneous candidiasis. N Engl. J. Med. 365, 54–61.

    PubMed  Article  Google Scholar 

  • Van der Meer, J.W., van de Veerdonk, F.L., Joosten, L.A., Kullberg, B.J., and Netea, M.G. 2010. Severe Candida spp. infections: new insights into natural immunity. Int. J. Antimicrob. Agents 36 Suppl 2, S58–62.

    Article  CAS  Google Scholar 

  • Verma, S. and Hefferman, M. 2008. Superficial fungal infection: dermatophytosis, onychomytosis, tinea nigra, piedra, pp. 1807–1821. In Wolff, K., Goldsmith, L., Katz, S., Gilchrest, B., Paller, A.S., and Leffell, D.J. (eds.). Fitzpatrick’s Dermatology in General Medicine. McGraw-Hill, New York, USA.

    Google Scholar 

  • Villar, C., Chukwuedum Aniemeke, J., Zhao, X.R., and Huynh-Ba, G. 2012. Induction of apoptosis in oral epithelial cells by Candida albicans. Mol. Oral Microbiol. 27, 436–448.

    PubMed  CAS  Article  Google Scholar 

  • Villar, C.C., Kashleva, H., Nobile, C.J., Mitchell, A.P., and Dongari-Bagtzoglou, A. 2007. Mucosal tissue invasion by Candida albicans is associated with e-cadherin degradation, mediated by transcription factor Rim101p and protease Sap5p. Infect. Immun. 75, 2126–2135.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Villar, C.C. and Zhao, X.R. 2010. Candida albicans induces early apoptosis followed by secondary necrosis in oral epithelial cells. Mol. Oral Microbiol. 25, 215–225.

    PubMed  CAS  Article  Google Scholar 

  • Villena, J., Salva, S., Agüero, G., and Alvarez, S. 2011. Immunomodulatory and protective effect of probiotic Lactobacillus casei against Candida albicans infection in malnourished mice. Microbiol. Immunol. 55, 434–445.

    PubMed  CAS  Article  Google Scholar 

  • Vylkova, S., Carman, A.J., Danhof, H.A., Collette, J.R., Zhou, H., and Lorenz, M.C. 2011. The fungal pathogen Candida albicans autoinduces hyphal morphogenesis by raising extracellular pH. MBio 2, 1–12.

    Article  CAS  Google Scholar 

  • Wächtler, B., Citiulo, F., Jablonowski, N., Förster, S., Dalle, F., Schaller, M., Wilson, D., and Hube, B. 2012. Candida albicans-epithelial interactions: dissecting the roles of active penetration, induced endocytosis and host factors on the infection process. PLoS One 7, e36952.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  • Wächtler, B., Wilson, D., Haedicke, K., Dalle, F., and Hube, B. 2011. From attachment to damage: defined genes of Candida albicans mediate adhesion, invasion and damage during interaction with oral epithelial cells. PLoS One 6, e17046

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  • Wagener, J., Weindl, G., de Groot, P.W.J., de Boer, A.D., Kaesler, S., Thavaraj, S., Bader, O., Mailänder-Sanchez, D., Borelli, C., Weig, M., et al. 2012. Glycosylation of Candida albicans cell wall proteins is critical for induction of innate immune responses and apoptosis of epithelial cells. PLoS One 7, e50518.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Weindl, G., Naglik, J.R., Kaesler, S., Biedermann, T., Hube, B., Korting, H.C., and Schaller, M. 2007. Human epithelial cells establish direct antifungal defense through TLR4-mediated signaling. J. Clin. Invest. 117, 3664–3672.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Weindl, G., Wagener, J., and Schaller, M. 2010. Epithelial cells and innate antifungal defense. J. Dent. Res. 89, 666–675.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Weindl, G., Wagener, J., and Schaller, M. 2011. Interaction of the mucosal barrier with accessory immune cells during fungal infection. Int. J. Med. Microbiol. 301, 431–435.

    PubMed  CAS  Article  Google Scholar 

  • Wheeler, R.T., Kombe, D., Agarwala, S.D., and Fink, G.R. 2008. Dynamic, morphotype-specific Candida albicans β-Glucan exposure during infection and drug treatment. PLoS Pathog. 4, e1000227.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  • White, T.C. 1997. Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus. Antimicrob. Agents Chemother. 41, 1482–1487.

    PubMed Central  PubMed  CAS  Google Scholar 

  • White, S., Larsen, B., and Virginia, H.W. 1997. Candida albicans morphogenesis is influenced by estrogen. Cell Mol. Life Sci. 53, 744–749.

    PubMed  CAS  Article  Google Scholar 

  • Williams, P. and Cámara, M. 2009. Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules. Curr. Opin. Microbiol. 12, 182–191.

    PubMed  CAS  Article  Google Scholar 

  • Williams, D.W., Jordan, R.P., Wei, X.Q., Alves, C.T., Wise, M.P., Wilson, M.J., and Lewis, M.A. 2013. Interactions of Candida albicans with host epithelial surfaces. J. Oral Microbiol. 5. doi: 10.3402/jom.v5i0.22434.

    Google Scholar 

  • Willment, J.A. and Brown, G.D. 2008. C-type lectin receptors in antifungal immunity. Trends Microbiol. 16, 27–32.

    PubMed  CAS  Article  Google Scholar 

  • Xie, Z., Thompson, A., Sobue, T., Kashleva, H., Xu, H., Vasilakos, J., and Dongari-Bagtzoglou, A. 2012. Candida albicans biofilms do not trigger reactive oxygen species and evade neutrophil killing. J. Infect. Dis. 206, 1936–1945.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Yan, L., Yang, C., and Tang, J. 2013. Disruption of the intestinal mucosal barrier in Candida albicans infections. Microbiol. Res. 168, 389–395.

    PubMed  CAS  Article  Google Scholar 

  • Yang, W., Yan, L., Wu, C., Zhao, X., and Tang, J. 2014. Fungal invasion of epithelial cells. Microbiol. Res. 169, 803–810.

    PubMed  CAS  Article  Google Scholar 

  • Yano, J., Lilly, E., Barousse, M., and Fidel, P.L. 2010. Epithelial cellderived S100 calcium-binding proteins as key mediators in the hallmark acute neutrophil response during Candida vaginitis. Infect. Immun. 78, 5126–5137.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Yarar, D., Waterman-Storer, C.M., and Schmid, S.L. 2005. A dynamic actin cytoskeleton functions at multiple stages of clathrinmediated endocytosis. Mol. Biol. Cell 16, 964–975.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Ye, P., Rodriguez, F.H., Kanaly, S., Stocking, K.L., Schurr, J., Schwarzenberger, P., Oliver, P., Huang, W., Zhang, P., Zhang, J., et al. 2001. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J. Exp. Med. 194, 519–527.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Zakikhany, K., Naglik, J.R., Schmidt-Westhausen, A., Holland, G., Schaller, M., and Hube, B. 2007. In vivo transcript profiling of Candida albicans identifies a gene essential for interepithelial dissemination. Cell. Microbiol. 9, 2938–2954.

    PubMed  CAS  Article  Google Scholar 

  • Zelante, T., Iannitti, R.G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., Zecchi, R., D’Angelo, C., Massi-Benedetti, C., Fallarino, F., et al. 2013. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39, 372–385.

    PubMed  CAS  Article  Google Scholar 

  • Zhang, M.X., Lupan, D.M., and Kozel, T.R. 1997. Mannan-specific immunoglobulin G antibodies in normal human serum mediate classical pathway initiation of C3 binding to Candida albicans. Infect. Immun. 65, 3822–3827.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Zhang, M.X. and Kozel, T.R. 1998. Mannan-specific immunoglobuling antibodies in normal human serum accelerate binding of C3 to Candida albicans via the alternative complement pathway. Infect. Immun. 66, 4845–4850.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Zhao, X., Oh, S.H., Cheng, G., Green, C., Nuessen, J., Yeater, K., Leng, R., Brown, A., and Hoyer, L. 2004. ALS3 and ALS8 represent a single locus that encodes a Candida albicans adhesin; functional comparisons between Als3p and Als1p. Microbiology 150, 2415–2428.

    PubMed  CAS  Article  Google Scholar 

  • Zhao, X., Oh, S.H., Yeater, K.M., and Hoyer, L.L. 2005. Analysis of the Candida albicans Als2p and Als4p adhesins suggests the potential for compensatory function within the Als family. Microbiology 151, 1619–1630.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Zhu, W. and Filler, S.G. 2010. Interactions of Candida albicans with epithelial cells. Cell. Microbiol. 12, 273–282.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Zhu, W., Phan, Q.T., Boontheung, P., Solis, N.V., Loo, J.A., and Filler, S.G. 2012. EGFR and HER2 receptor kinase signaling mediate epithelial cell invasion by Candida albicans during oropharyngeal infection. Proc. Natl. Acad. Sci. USA 109, 14194–14199.

    PubMed Central  PubMed  CAS  Article  Google Scholar 

  • Zipfel, P.F., Skerka, C., Kupka, D., and Luo, S. 2011. Immune escape of the human facultative pathogenic yeast Candida albicans: the many faces of the Candida Pra1 protein. Int. J. Med. Microbiol. 301, 423–430.

    PubMed  CAS  Article  Google Scholar 

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Authors and Affiliations

  1. Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knoell-Institute, Jena, Germany

    Sarah Höfs, Selene Mogavero & Bernhard Hube

  2. Friedrich Schiller University, Jena, Germany

    Bernhard Hube

  3. Center for Sepsis Control and Care, University Hospital, Jena, Germany

    Bernhard Hube

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  1. Sarah Höfs
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Höfs, S., Mogavero, S. & Hube, B. Interaction of Candida albicans with host cells: virulence factors, host defense, escape strategies, and the microbiota. J Microbiol. 54, 149–169 (2016). https://doi.org/10.1007/s12275-016-5514-0

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Keywords

  • host response
  • fungal infection
  • adhesion
  • morphogenesis
  • biofilm
  • fungal-bacterial interactions