Back
 PP  Vol.2 No.4 , October 2011
Basic Research – Significance of Detection and Clinical Impact of Candida albicans in Non-Immunosuppressed Patients
Abstract: Background: The clinical significance of the detection of Candida albicans on mucous membranes of the respiratory or intestinal tract from patients in intensive care units is still not finally clarified. Many patients reveal colonization, although, despite increased risk, there are only a few invasive infections detectable. Therefore, antimycotic therapy in this setting is strongly discouraged. In reality, however, many patients receive antimycotics as a pre-emptive therapy. To elucidate this point, a literature research was performed. Results: In the light of new results on the pathogenicity of C.albicans, the recommendation not to treat should be discussed anew. Without becoming invasive, C.albicans influences the immune system negatively in an anti-inflammatory sense (Th2) by means of at least two distinct mechanisms [action on toll like receptors (TLR), production of farnesol], which will be discussed. Conclusion: It is believed that patients in the phase of CARS or MARS can be further endangered by concomitant colonization of mucous membranes by C.albicans, i.e., in the sense of an anti-inflammatory immune response. Treatment with azole preparations, like fluconazole, which interacts with ergosterol synthesis in this phase of the disease, may trigger an additional effect on the patient, through increase of farnesol concentration by way of a negative feedback. Results of animal experiments on the immune system and concomitant therapeutic consequences indicate the need for verification through clinical trials.
Cite this paper: nullP. Heizmann, F. Klefisch and W. Heizmann, "Basic Research – Significance of Detection and Clinical Impact of Candida albicans in Non-Immunosuppressed Patients," Pharmacology & Pharmacy, Vol. 2 No. 4, 2011, pp. 354-360. doi: 10.4236/pp.2011.24046.
References

[1]   E.L. Keeney, “Pulmonary mycotic infections; allergic and immunologic factors”, Calif Med, Vol. 81, No. 6, 1954, pp. 367-378.

[2]   J. Rello, M.E. Esandi, E. Diaz, D. Mariscal, M. Gallego, J. Valles, “The role of Candida sp isolated from bronchoscopic samples in nonneutropenic patients”, Chest, Vol. 114, No.1, 1998, pp. 146-149.

[3]   J. Barenfanger, P. Arakere, R.D. Cruz, A. Imran, C. Drake, J. Lawhorn, S.J. Verhulst, N. Khardori, “Improved outcomes associated with limiting identification of Candida spp. in respiratory secretions”, J Clin Microbiol, Vol. 41, No. 12, 2003, pp. 5645-5649.

[4]   D. Pittet, M. Monod, P.M. Suter, E. Frenk, R. Auckenthaler, “Candida colonization and subsequent infections in critically ill surgical patients”, Ann Surg, Vol. 220, No. 6, 1994, pp. 751-758.

[5]   D.R. Reagan, M.A. Pfaller, R.J. Hollis, R.P. Wenzel, “Characterization of the sequence of colonization and nosocomial candidemia using DNA fingerprinting and a DNA probe”, J Clin Microbiol, Vol. 28, No. 12, 1990, pp. 2733-2738.

[6]   A. Voss, R.J. Hollis, M.A. Pfaller, R.P. Wenzel, B.N. Doebbeling, “Investigation of the sequence of colonization and candidemia in nonneutropenic patients”, J Clin Microbiol, Vol. 32, No. 4, 1994, pp. 975-980.

[7]   M. Laverdiere, A.C. Labbe, C. Restieri, C. Rotstein, D. Heyland, S. Madger, T. Stewart, “Susceptibility patterns of Candida species recovered from Canadian intensive care units” J Crit Care, Vol. 22, No. 3, 2007, pp. 245- 250.

[8]   C. Leon, S. Ruiz-Santana, P. Saavedra, B. Almirante, J. Nolla-Salas, F. Alvarez-Lerma, J. Garnacho-Montero, M.A. Leon, “A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization”, Crit Care Med, Vol. 34, No. 3, 2006, pp. 730-737.

[9]   J. Savolainen, M. Viander, A. Koivikko, “IgE-, IgA- and IgG-antibody responses to carbohydrate and protein antigens of Candida albicans in asthmatic children.”, Allergy, Vol. 45, No. 1, 1990, pp. 54-63.

[10]   J. Savolainen, “A standardized densitometric immunoblotting analysis of Candida albicans protein allergens”, Clin Exp Allergy, Vol. 25, No. 4, 1995, pp. 357-363.

[11]   K. Ito, A. Ishiguro, T. Kanbe, K. Tanaka, S. Torii, “Detection of IgE antibody against Candida albicans enolase and its crossreactivity to Saccharomyces cerevisiae enolase”, Clin Exp Allergy, Vol. 25, No. 6, 1995, pp. 522- 528.

[12]   L. Tonnetti, R. Spaccapelo, E. Cenci, A. Mencacci, P. Puccetti, R.L. Coffman, F. Bistoni, L. Romani, “Interleukin-4 and -10 exacerbate candidiasis in mice”, Eur J Immunol, Vol. 25, No. 6, 1995, pp. 1559-1565.

[13]   G. Talluri, V.K. Marella, D. Shirazian, G.J. Wise, “Immune response in patients with persistent candiduria and occult candidemia” J Urol, Vol. 162, No. 4, 1999, pp. 1361-1364.

[14]   D. Lilic, I. Gravenor, N. Robson, D.A. Lammas, P. Drysdale, J.E. Calvert, A.J. Cant, M. Abinun, “Deregulated production of protective cytokines in response to Candida albicans infection in patients with chronic mucocutaneous candidiasis”, Infect Immun, Vol. 71, No. 10, 2003, pp. 5690-5699.

[15]   M.G. Netea, R. Sutmuller, C. Hermann, C.A. van der Graaf, J.W. van der Meer, J.H. van Krieken, T. Hartung, G. Adema, B.J. Kullberg, “Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells”, J Immunol, Vol. 172, No. 6, 2004, pp. 3712-3718.

[16]   A. Vazquez-Torres, J. Jones-Carson, R.D. Wagner, T. Warner, E. Balish, “Early resistance of interleukin-10 knockout mice to acute systemic candidiasis”, Infect Immun, Vol. 67, No. 2, 1999, pp. 670-674.

[17]   S. Dillon, S. Agrawal, K. Banerjee, J. Letterio, T.L. Denning, K. Oswald-Richter, D.J. Kasprowicz, K. Kellar, J. Pare, T. van Dyke, S. Ziegler, D. Unutmaz, B. Pulendran, ?Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance” J Clin Invest, Vol. 116, No. 4, 2006, pp. 916-928.

[18]   M.G. Netea, F. van de Veerdonk, I. Verschueren, J.W. van der Meer, B.J. Kullberg, “Role of TLR1 and TLR6 in the host defense against disseminated candidiasis”, FEMS Immunol Med Microbiol, Vol. 52, No.1, 2008, pp. 118- 123.

[19]   C.A. van der Graaf, M.G. Netea, I. Verschueren, J.W. van der Meer, B.J. Kullberg, “Differential cytokine production and Toll-like receptor signaling pathways by Candida albicans blastoconidia and hyphae”, Infect Immun, Vol. 73, No. 11, 2005, pp. 7458-7464.

[20]   D.D. Mosel, R. Dumitru, J.M. Hornby, A.L. Atkin, K.W. Nickerson, “Farnesol concentrations required to block germ tube formation in Candida albicans in the presence and absence of serum”, Appl Environ Microbiol, Vol. 71, No. 8, 2005, pp. 4938-4940.

[21]   J.M. Hornby, E.C. Jensen, A.D. Lisec, J.J. Tasto, B. Jahnke, R. Shoemaker, P. Dussault, K.W. Nickerson, “Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol” Appl Environ Microbiol, Vol. 67, No. 7, 2001, pp. 2982-2992.

[22]   D.H. Navarathna, K.W. Nickerson, G.E. Duhamel, T.R. Jerrels, T.M. Petro, “Exogenous farnesol interferes with the normal progression of cytokine expression during candidiasis in a mouse model”, Infect Immun 2007, 75(8): 4006-4011.

[23]   C. Westwater, E. Balish, D.A. Schofield, “Candida albicans-conditioned medium protects yeast cells from oxidative stress: a possible link between quorum sensing and oxidative stress resistance”, Eukaryot Cell, Vol. 4, No. 10, 2005, pp. 1654-1661.

[24]   A. Deveau, A.E. Piispanen, A.A. Jackson, D.A. Hogan, “Farnesol induces hydrogen peroxide resistance in Candida albicans yeast by inhibiting the ras-cyclic AMP signaling pathway”, Eukaryotic Cell, Vol. 9, No. 4, 2010, pp. 569-577.

[25]   D.H. Navarathna, J.M. Hornby, N. Hoerrmann, A.M. Parkhurst, G.E. Duhamel, K.W. Nickerson, “Enhanced pathogenicity of Candida albicans pre-treated with subinhibitory concentrations of fluconazole in a mouse model of disseminated candidiasis”, J Antimicrob Chemother, Vol. 56, No. 6, 2005, pp. 1156-1159.

[26]   D.H. Navarathna, J.M. Hornby, N. Krishnan, A. Parkhurst, G.E. Duhamel, K.W. Nickerson, “Effect of farnesol on a mouse model of systemic candidiasis, determined by use of a DPP3 knockout mutant of Candida albicans”, Infect Immun, Vol. 75, No. 4, 2007, pp. 1609-1618.

[27]   Y.Y. Cao, Y.B. Cao, Z. Xu, K. Ying, Y. Li, Y. Xie, Z.Y. Zhu, W.S. Chen, Y.Y. Jiang, “cDNA microarray analysis of differential gene expression in Candida albicans biofilm exposed to farnesol”, Antimicrob Agents Chemother, Vol. 49, No. 2, 2005, pp. 584-589.

[28]   J.M. Hornby, K.W. Nickerson, “Enhanced production of farnesol by Candida albicans treated with four azoles”, Antimicrob Agents Chemother, Vol. 48, No. 6, 2004, pp. 2305-2307.

[29]   S. Abe, R. Tsunashima, R. Iijima, T. Yamada, N. Maruyama, T. Hisajima, Y. Abe, H. Oshima, M. Yamazaki, “Suppression of anti-Candida activity of macrophages by a quorum-sensing molecule, farnesol, through induction of oxidative stress”, Microbiol Immunol, Vol. 53, No. 6, 2009, pp. 323-330.

[30]   M.A. Scheper, M.E. Shirtliff, T.F. Meiller, B.M. Peters, M.A. Jabra-Rizk, “Farnesol, a fungal quorum-sensing molecule triggers apoptosis in human oral squamous carcinoma cells”, Neoplasia, Vol. 10, No. 9, 2008, pp. 954- 963.

[31]   R. Dumitru, J.M. Hornby, K.W. Nickerson, “Defined anaerobic growth medium for studying Candida albicans basic biology and resistance to eight antifungal drugs”, Antimicrob Agents Chemother, Vol. 48, No. 7, 2004, pp. 2350-2354.

[32]   T. Hisajima, N. Maruyama, Y. Tanabe, H. Ishibashi, T. Yamada, K. Makimura, Y. Nishiyama, K. Funakoshi, H. Oshima, S. Abe, “Protective effects of farnesol against oral candidiasis in mice”, Microbiol Immunol, Vol. 52, No. 7, 2008, pp. 327-333.

[33]   T.M. Weissenbacher, S.S. Witkin, A. Gingelmaier, C. Scholz, K. Friese, I. Mylonas, “Relationship between recurrent vuvovaginal candidosis and immune mediators in vaginal fluid”, Eur J Obstet Gynecol Reprod Biol, Vol. 144, No. 1, 2009, pp. 59-63.

[34]   S.M. Chabot, T.S. Chernin, M. Shawi, J. Wagner, S. Farrant, D.S. Burt, C. Cyr, M.R. Neutra, “TLR2 activation by proteosomes promotes uptake of particulate vaccines at mucosal surfaces”, Vaccine, Vol. 25, No. 29, 2007, pp. 5348-5358.

[35]   M.R. Mainous, W. Ertel, I.H. Chaudry, E.A. Deitch, “The gut: a cytokine-generating organ in systemic inflammation?”, Shock, Vol. 4, No. 3, 1995, pp. 193-199.

[36]   E. Mavromanolakis, S. Maraki, A. Cranidis, Y. Tselentis, D.P. Kontoyiannis, G. Samonis, “The impact of norfloxacin, ciprofloxacin and ofloxacin on human gut colonization by Candida albicans”, Scand J Infect Dis, Vol. 33, No. 6, 2001, pp. 477-478.

[37]   G. Samonis, H. Anastassiadou, M. Dassiou, Y. Tselentis, G.P. Bodey, “Effects of broad-spectrum antibiotics on colonization of gastrointestinal tracts of mice by Candida albicans”, Antimicrob Agents Chemother, Vol. 38, No. 3, 1994, pp. 602-603.

[38]   A. Oberholzer, C. Oberholzer, L.L. Moldawer, “Sepsis syndromes: understanding the role of innate and acquired immunity”, Shock, Vol. 16, No. 2, 2001, pp. 83-96.

[39]   R.S. Hotchkiss, I.E. Karl, “The pathophysiology and treatment of sepsis”, N Engl J Med, Vol. 348, No. 2, 2003, pp. 138-150.

[40]   A. Katragkou, A. Chatzimoschou, M. Simitsopoulou, M. Dalakiouridou, E. Diza-Mataftsi, C. Tsantali, E. Roilides, “Differential activities of newer antifungal agents against Candida albicans and Candida parapsilosis biofilms”, Antimicrob Agents Chemother, Vol. 52, No. 1, 2008, pp. 357-360.

[41]   R.T. Wheeler, G.R. Fink, “A drug-sensitive genetic network masks fungi from the immune system”, PLoS Pathog, Vol. 2, No. 4, 2006, e35. www.10.1371/journal.ppat.0020035

[42]   A.C. Reboli, C. Rotstein, P.G. Pappas, S.W. Chapman, D.H. Kett, D. Kumar, R. Betts, M. Wible, B.P. Goldstein, J. Schranz, D.S. Krause, T.J. Walsh, “Anidulafungin versus fluconazole for invasive candidiasis”, N Engl J Med, Vol. 356, No. 24, 2007, pp. 2472-2482.

 
 
Top