To determine the frequency and expression of the ten SAP (secreted aspartyl protease) genes in a group of Candida albicans strains isolated from Mexican women suffering from vaginal candidosis, a group of 264 women (age 18-57 years) with vaginal infections, predisposed by diabetes mellitus or contraceptive consumption, were evaluated. C. albicans was identified using PCR to amplify the rRNA internal transcribed spacer regions ITS1 and ITS2. The presence of the SAP genes was determined using conventional PCR, and their expression levels were determined using real-time PCR after the C.albicans strains had been grown in reconstituted human vaginal epithelium (RHVE). C. albicans was identified in the samples from 50 women (18.9%). The genotyping frequencies of the SAP genes were as follows: SAP1,94%; SAP2,98%; SAP3,80%; SAP4,100%; SAP5,100%; SAP6,100%; SAP7,63%; SAP8,96%; SAP9,70%; and SAP10, 88%. The most frequently expressed genes in the strains harboring all of the genes were SAP1,90%; SAP2,90%; SAP3,90%; SAP4, 100%; SAP5,90%; SAP6,90%; SAP7,100%; SAP8, 90%; SAP9, 100%; and SAP10, 100%. SAP genes were expressed in the RHVE, suggesting that the Sap proteins play an important role in the pathogenesis of infection.
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E. Monroy-Pérez, G. Paniagua-Contreras, F. Vaca-Paniagua, E. Negrete-Abascal and S. Vaca, "SAP Expression in Candida albicans Strains Isolated from Mexican Patients with Vaginal Candidosis," International Journal of Clinical Medicine, Vol. 4 No. 1, 2013, pp. 25-31. doi: 10.4236/ijcm.2013.41006.
 F. C. Odds, N. A. R. Gow and A. J. P. Brown, “Towards a Molecular Understanding of Candida albicans Virulence,” In: J. Heitman, S. G. Filler, J. E. Edwards Jr and A. P. Mitchell, Eds. Molecular Principles of Fungal Patho-genicity, ASM Press, Washington, 2006, pp. 305-319.
 B. Foxman, J. V. Marsh, B. Gillespie and J. D. Sobel, “Frequency and Response to Vaginal Symptoms among White and African American Women: Results of a Random Digit Dialing Survey,” Journal Women’s Health, Vol. 7, No. 9, 1998, pp. 1167-1174.
 J. D. Sobel, S. Faro, R. W. Force, B. Foxman, W. J. Ledger, P. R. Nyirsejy, B. D. Reed and P. R. Summers, “Vulvovaginal Candidiasis: Epidemiologic, Diagnostic, and Therapeutic Considerations,” American Journal of Obstetricts and Gynecology, Vol. 178, No. 2, 1998, pp. 203-211. doi:10.1016/S0002-9378(98)80001-X
 J. D. Sobel, “Vaginitis,” New England Journal of Medicine, Vol. 337, No. 26, 1997, pp. 1896-1903.
 J. D. Sobel, G. Muller and H. R. Buckley, “Critical Role of Germ Tube Formation in the Pathogenesis of Candidal Vaginitis,” Infection and Immunity, Vol. 44, No. 3, 1984, pp. 576-580.
 D. R. Soll, C. J. Langtimm, J. McDowell, J. Hicks and R. Galask, “High-Frequency Switching in Candida Strains Isolated from Vaginitis Patients,” Journal of Clinical Microbiology, Vol. 25, No. 9, 1987, pp. 1611-1622.
 J. Hellstein, H. Vawter-Hugart, P. Fotos, J. Schmid and D. R. Soll, “Genetic Similarity and Phenotypic Diversity of Commensal and Pathogenic Strains of Candida albicans Isolated from the Oral Cavity,” Journal of Clinical Microbiology, Vol. 31, No. 12, 1993, pp. 3190-3199.
 K. Vargas, S. A. Messer, M. Pfaller, S. R. Lockhart, J. T. Stapleton, J. Hellstein and D. R. Soll, “Elevated Phenotypic Switching and Drug Resistance of Candida albicans from Human Immunodeficiency Virus-Positive Individuals Prior to First Thrush Episode,” Journal of Clinical Microbiology, Vol. 38, No. 10, 2000, pp. 3595-3607.
 N. K. Gaur and S. A. Klotz, “Expression, Cloning, and Characterization of a Candida albicans Gene, ALA1, That Confers Adherence Properties upon Saccharomyces cerevisiae for Extracellular Matrix Proteins,” Infection and Immunity, Vol. 65, No. 12, 1997, pp. 5289-5294.
 L. L. Hoyer and J. E. Hecht, “The ALS5 Gene of Candida albicans and Analysis of the Als5p N-Terminal Domain,” Yeast, Vol. 18, No. 1, 2001, pp. 49-60.
 X. Zhao, C. Pujol, D. R. Soll and L. L. Hoyer, “Allelic Variation in the Contiguous Loci Encoding Candida albicans ALS5, ALS1 and ALS9,” Microbiology, Vol. 149, No. 10, 2003, pp. 2947-2960. doi:10.1099/mic.0.26495-0
 X. Zhao, S. H. Oh, G. Cheng, C. B. Green, J. A. Nuessen, K. Yeater, R. P. Leng, A. J. Brown and L. L. Hoyyer, “ALS3 and ALS8 Represent a Single Locus That Encodes a Candida albicans Adhesin; Functional Comparisons between Als3p and Als1p,” Microbiology, Vol. 150, No. 7, 2004, pp. 2415-2428. doi:10.1099/mic.0.26943-0
 B. Hube, “Possible Role of Secreted Proteinases in Candida albicans Infection,” Revista Iberoamericana de Micologia, Vol. 15, No. 2, 1998, pp. 65-68.
 M. A. Ghannoum, “Potential Role of Phospholipases in Virulence and Fungal Pathogenesis,” Clinical Microbiology Reviews, Vol. 13, No. 1, 2000, pp. 122-143.
 B. Hube and J. Naglik, “Candida albicans Proteinases: Resolving the Mystery of a Gene Family,” Microbiology, Vol. 147, No. 8, 2001, pp. 1997-2005.
 M. Schaller, H. C. Korting, W. Schafer, J. Bastert, W. Chen and B. Hube, “Secreted Aspartic Proteinase (Sap) Activity Contributes to Tissue Damage in a Model of Human Oral Candidiasis,” Molecular Microbiology, Vol. 34, No. 1, 1999, pp. 169-180.
 M. Borgvon Zepelin, S. Beggah, K. Boggian, D. Sanglard and M. Monod, “The Expression of the Secreted Aspartyl Proteinases Sap4 to Sap6 from Candida albicans in Murine Macrophages,” Molecular Microbiology, Vol. 28, No. 3, 1998, pp. 543-554.
 M. Borgvon Zepelin, I. Meyer, R. Thomssen, R. Würzner, D. Sanglard, A. Telenti and M. Monod, “HIV-Protease Inhibitors Reduce Cell Adherence of Candida albicans Strains by Inhibition of Yeast Secreted Aspartic Proteases,” The Journal of investigative dermatology, Vol. 113, No. 5, 1999, pp.747-751.
 T. C. White and N. Agabian, “Candida albicans Secreted Aspartyl Proteinases: Isoenzyme Pattern Is Determined by Cell Type, and Levels Are Determined by Environmental Factors,” Journal of Bacteriology, Vol. 177, No. 18, 1995, pp. 5215-5221.
 B. Hube, M. Monod, D. A. Schofield, A. J. P. Brown and N. A. R. Gow, “Expression of Seven Members of the Gene Family Encoding Secretory Aspartyl Proteinases in Candida albicans,” Molecular Microbiology, Vol. 14, No. 1, 1994, pp. 87-99.
 M. Schaller, W. Schafer, H. C. Korting and B. Hube, “Differential Expression of Secreted Aspartyl Proteinases in a Model of Human Oral Candidiasis and in Patient Samples from the Oral Cavity,” Molecular Microbiology, Vol. 29, No. 2, 1998, pp. 605-615.
 J. R. Naglik, C. A. Rodgers, P. J. Shirlaw. J. L. Dobbie, L. L. Fernandes-Naglik, D. Greenspan, N. Agabian and S. J. Challacombe, “Differential Expression of Candida albicans Secreted Aspartyl Proteinase and Phospholipase B Genes in Humans Correlates with Active Oral and Vaginal Infections,” Journal of Infectious Diseases, Vol. 188, No. 3, 2003, pp. 465-475.
 F. De Bernardis, S. Arancia, L. Morelli, B. Hube, D. Sanglard, W. Schafer and A. Cassone, “Evidence That Members of the Secretory Aspartyl Proteinase Gene Family, In Particular SAP2, Are Virulence Factors for Candida Vaginitis,” Journal of Infectious Diseases, Vol. 179, No. 1, 1999, pp. 201-208. doi:10.1086/314546
 F. De Bernardis, A. Cassone, J. Sturtevant and R. Calderone, “Expression of Candida albicans SAP1 and SAP2 in Experimental Vaginitis,” Infection and Immunity, Vol. 63, No. 5, 1995, pp. 1887-1892.
 D. Sanglard, B. Hube, M. Monod, F. C. Odds, and N. A. Gow, “A Triple Deletion of the Secreted Aspartyl Proteinase Genes SAP4, SAP5, and SAP6 of Candida albicans Causes Attenuated Virulence,” Infection and Immunity, Vol. 65, No. 9, 1997, pp. 3539-3546.
 F. De Bernardis, P. A. Sullivan and A. Cassone, “Aspartyl Proteinases of Candida albicans and Their Role in Pathogenicity,” Medical Mycology, Vol. 39, No. 4, 2001, pp. 303-313. doi:10.1080/714031039
 J. D. Sobel, A. Hasegawa, F. Debernardis, D. Adriani, G. Pellegrini, A. Cassone, P. L. Fidel, C. G. Haidaris, F. Gigliotti, A. G. Harmsen, S. Fujita, K. Yamamoto, K. Makimura, K. Shibuya, K. Uchida and H. Yamaguchi, “Selected Animal Models: Vaginal Candidosis, Pneumocystis Pneumonia, Dermatophytosis and Trichosporosis,” Medical Mycology, Vol. 36, No. 1, 1998, pp. 129-136.
 L. Guizhen and T. G. Mitchell, “Rapid Identification of Pathogenic Fungi Directly from Cultures by Using Multiplex PCR,” Journal of Clinical Microbiology, Vol. 40, No. 8, 2002, pp. 2860-2865.
 B. Hube, C. J. Turver, F. C. Odds, H. Heiffert, G. J. Boulnois, H. Kochel and R. Rüchel, “Sequence of the Candida albicans Gene Encoding the Secretory Aspartate Proteinase,” Journal of Medical and Veterinary Mycology, Vol. 29, No. 2 1991, pp. 129-132.
 R. J. Wright, A. Carne, A. D. Hieber, I. L. Lamont, G. W. Emerson and A. A. Sullivan, “A Second Gene for a Secreted Aspartate Proteinase in Candida albicans,” Journal of Bacteriology, Vol. 174, No. 23, 1992, pp. 7848- 7853.
 T. C. White, S. H. Miyasaki and N. Agabian, “Three Distinct Secreted Aspartyl Proteinases in Candida albicans,” Journal of Bacteriology, Vol. 175, No. 19, 1993, pp. 6126-6133.
 M. Monod, G. Togni, B. Hube and D. Sanglard, “Multiplicity of Genes Encoding Secreted Aspartic Proteinases in Candida Species,” Molecular Microbiology, Vol. 13, No. 2, 1994, pp. 357-368.
 J. R. Naglik, D. Moyes, J. Makwana, K. Kanzaria, E. Tsichlaki, G. Wendl, A. R. Tappuni, C. A. Rodgers, A. J. Woodman, S. J. Challacombe, M. Schaller and B. Hube, “Quantitative Expression of the Candida albicans Secreted Aspartyl Proteinase Gene Family in Human Oral and Vaginal Candidiasis,” Microbiology, Vol. 154, No. 11, 2008, pp. 3266-3280. doi:10.1099/mic.0.2008/022293-0
 A. M. Geiger, B. Foxman and B. W. Gillespie, “The Epidemiology of Vulvovaginal Candidiasis among University Students,” American Journal of Public Health, Vol. 85, No. 8, 1995, pp. 1146-1148.
 M. Geiger and B. Foxman, “Risk Factors for Vulvovaginal Candidiasis: A Case-Control Study among University Students,” Epidemiology, Vol. 7, No. 2, 1996, pp. 182-187. doi:10.1097/00001648-199603000-00013
 J. D. Sobel, “Vulvovaginitis in Healthy Women,” Comprehensive Therapy, Vol. 25, No. 6, 1999, pp. 335-346.
 J. D. Sobel, “Epidemiology and Pathogenesis of Recurrent Vulvovaginal Candidiasis,” American Journal of Obstetrics and Gynecology, Vol. 152, No. 7, 1985, pp. 924-935.
 J. R. Naglik, S. J. Challacombe and B. Hube, “Candida albicans Secreted Aspartyl Proteinases in Virulence and Pathogenesis,” Microbiology and Molecular Biology Reviews, Vol. 67, No. 3, 2003, pp. 400-428.
 A. R. Colina, F. Aumont, N. Deslauriers, P. Belhumeur and L. de Repentigny, “Evidence for Degradation of Gastrointestinal Mucin by Candida albicans Secretory Aspartyl Proteinase,” Infection and Immunity, Vol. 64, No. 11, 1996, pp. 4514-4519.
 L. de Repentigny, F. Aumont, K. Bernard and P. Belhumeur, “Characterization of Binding of Candida albicans to Small Intestinal Mucin and Its Role in Adherence to Mucosal Epithelial Cells,” Infection and Immunity, Vol. 68, No. 6, 2000, pp. 3172-3179.
 R. Rüchel, “Cleavage of Immunoglobulins By Pathogenic Yeasts of the Genus Candida,” Microbiological Sciences, Vol. 3, No. 10, 1986, pp. 316-319.
 B. Hube, “Candida albicans Secreted Aspartyl Proteinases,” Current Topics in Medical Mycology, Vol. 7, No. 1, 1996, pp. 55-59.
 D. M. Ogrydziak, “Yeast Extracellular Proteases,” Critical Reviews in Biotechnology, Vol. 13, No. 1, 1993, pp. 1-55. doi:10.3109/07388559309069197
 T. L. Ray and C. D. Payne, “Comparative Production and Rapid Purification of Candida Acid Proteinase from Protein-Supplemented Cultures,” Infection and Immunity, Vol. 58, No. 2, 1990, pp. 508-4514.
 J. Morschhauser, R. Virkola, T. K. Korhonen and J. Hacker, “Degradation of Human Subendothelial Extracellular Matrix by Proteinase-Secreting Candida albicans,” FEMS Microbiology Letters, Vol. 153, No. 2, 1997, pp. 349-355.
 M. Schaller, M. Bein, C. H. Korting, S. Baur, G. Hamm, M. Monod, S. Beinhauer and B. Hube, “The Secreted Aspartyl Proteinases Sap1 and Sap2 Cause Tissue Damage in an in Vitro Model of Vaginal Candidiasis Based on Reconstituted Human Vaginal Epithelium,” Infection and Immunity, Vol. 71, No. 6, 2003, pp. 3227-3234.
 H. L. Cui and D. L. Wei, “Differential Expression of Candida albicans Secreted Aspartyl Proteinase in Human Vulvovaginal Candidiasis,” Mycoses, Vol. 50, No. 5, 2008, pp. 383-390.
 G. Newport and N. Agabian, “KEX2 Influences Candida albicans Proteinase Secretion and Hyphal Formation,” The Journal of Biological Chemistry, Vol. 272, No. 46, 1997, pp. 28954-28961. doi:10.1074/jbc.272.46.28954