Factores de virulencia y su efecto sobre la sensibilidad a los fármacos antifúngicos de Candida albicans causante de vulvovaginitis candidiásica recurrente.
Virulence factors and their effect on antifungal sensitivity of Candida albicans causing recurrent vulvovaginal candidiasis.
Keywords:
Candida albicans, Vulvovaginitis, Virulence, Susceptibility, Fluconazole, Voriconazole, Amphotericin B.
Abstract
Candidal vulvovaginitis (CVV) is mainly caused by Candida albicans. The activities of phospholipases, proteases, hemolysins, and biofilms were evaluated as virulence factors in C. albicans causing recurrent CVV, and their effects on antifungal susceptibility were assessed to understand their influence on antifungal sensitivity. A total of 22 C. albicans strains isolated from patients with recurrent CVV who attended the Microbiology Department of the La Floresta Medical Institute, Caracas–Venezuela, from July 2023 to June 2024 were analyzed. Phospholipase, protease, and hemolysin activity, along with biofilm formation and the minimum inhibitory concentration (MIC) susceptibility profiles for fluconazole, voriconazole, and amphotericin B, were determined using the Vitek 2 Compact® assay with the AST-YSO1® card. All strains produced hemolysins; 77% exhibited phospholipase activity, and 27.3% expressed prote- ases. 82% were capable of forming biofilms. Resistance rates were 82% for flu- conazole and 73% for voriconazole; all strains were susceptible to amphotericin
- There was no statistically significant relationship between the three drugs tested and the virulence factors studied. Virulence factors are independent vari- ables in the antifungal susceptibility profile but participate in different stages of infection and are associated with the clinical presentation of CVV.
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References
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Mohammadi F, Ghasemi Z, Familsatarian B, Salehi E, Sharifynia S, Barikani A, et al. Relationship between antifungal susceptibility profile and virulence factors in Candida albicans isolated from nail specimens. Rev Soc Bras Med Trop. 2020; 53: e20190214. https://doi.org/10.1590/0037-8682-0214-2019.
Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clin Microbiol Rev. 2010; 23(2):253-273. https://doi.org/10.1128/cmr.00076-09.
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Sobel JD, Sobel R. Current treatment options for vulvovaginal candidiasis caused by azole-resistant Candida species. Expert Opin Pharmacother. 2018; 19(9):971-977. https://doi.org/10.1080/14656566.2018.1476490.
Sriphannam C, Nuanmuang N, Saengsawang K, Amornthipayawong D, Kummasook A. Anti-fungal susceptibility and virulence factors of Candida spp. isolated from blood cultures. J Mycol Med. 2019; 29(4):325-330. https://doi.org/10.1016/j.mycmed.2019.08.001.
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Aoki S, Ito-Kuwa S, Nakamura Y, Masuhara T. Comparative pathogenicity of wild-type strains and respiratory mutants of Candida albicans in mice. Zentralbl Bakteriol. 1990; 273:332-343. https://doi.org/10.1016/S0934-8840(11)80437-8.
Cruz Choappa R, Vieille Oyarzo P. Nuevos nombres para antiguas especies fúngicas de importancia médica. Rev Chil Infectol. 2023; 40(5): 461-464. http://doi.org/10.4067/s0716-10182023000500461.
De Melo Riceto ÉB, de Paula Menezes R, Penatti MPA, dos Santos Pedroso R. Enzymatic and hemolytic activity in different Candida species. Rev Iberoam Micol. 2015; 32(2):79-82. https://doi.org/10.1016/j.riam.2013.11.003.:79-82.
Ortolan Rörig KC, Colacite J, Abegg MA. Produção de fatores de virulência in vitro por espécies patogênicas do gênero Candida. Rev Soc Bras Med Trop. 2009; 42(2):225-227. https://doi.org/10.1590/S0037-86822009000200029.
de Paula Menezes R, de Melo Riceto ÉB, Borges AS, de Brito Roder DV, dos Santos Pedroso R. Evaluation of virulence factors of Candida albicans isolated from HIV-positive individuals using HAART. Arch Oral Biol. 2016; 66:61-65. https://doi.org/10.1016/j.archoralbio.2016.02.004.
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Stepanovic S, Vukovic D, Dakic I, Savic B, Svabic-Vlahovic M. A modified micro-titer-plate test for quantification of staphylococcal biofilm formation. J Microbiol Methods. 2000; 40(2):175-179. https://doi.org/10.1016/s0167-7012(00)00122-6.
Ochiuzzi ME, Arechavala A, Guelfand L, Maldonado I, Soloaga R, Red de Micología CABA, Argentina. Evaluación de las tarjetas AST-YSO1 del sistema Vitek 2 para determinar la sensibilidad a antifúngicos de levaduras del género Candida. Rev Argent Microbiol. 2014; 46(2):111-118. https://doi.org/10.1016/S0325-7541(14)70058-6.
Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antifungal Susceptibility Testing of Yeasts. 2nd ed. CLSI Supplement M60- Ed 2. Wayne, PA: Clinical and Laboratory Standards Institute; 2020. Disponible en: https://www.clsi.org.
Pfaller MA, Espinel-Ingroff A, Canton E, Castanheira M, Cuenca-Estrella M, Diekema DJ, et al. Wild-type MIC distributions and epidemiological cutoff values for amphotericin B, flucytosine, and itraconazole and Candida spp. as determined by CLSI broth microdilution. J Clin Micro-biol. 2012; 50(6):2040-2046. https://doi.org/10.1128/JCM.00248-12.
Hube B. From commensal to pathogen: stage and tissue-specific gene expression of Candida albicans. Curr Opin Microbiol. 2004;7(4):336–341. https://doi.org/10.1016/j.mib.2004.06.003.
Jacobsen ID. The role of host and fungal factors in the commensal-to-pathogen transition of Candida albicans. Curr Clin Microbiol Rep. 2023; 10(2):55-65. https://doi.org/10.1007/s40588-023-00190-w.
Samaranayake LP, Raeside JM, Macfarlane TW. Factors affecting the phospholipase activity of Candida species in vitro. Sabouraudia. 1984; 22(3):201-207. https://doi.org/10.1080/00362178485380331.
Pandey N, Gupta MK, Tilak R. Extracellular hydrolytic enzyme activities of the different Candida spp. isolated from the blood of the intensive care unit-admitted patients. J Lab Physicians. 2018; 10(4):392-396. https://doi.org/10.4103/JLP.JLP_81_18.
Hernández-Solís SE, Rueda-Gordillo F, Rojas-Herrera RA. Actividad de la proteinasa en cepas de Candida albicans aisladas de la cavidad oral de pacientes inmunodeprimidos, con candidiasis oral y sujetos sanos. Rev Iberoam Micol. 2014; 31(2):137-140. https://doi.org/10.1016/j.riam.2013.09.003.
Tiwari P, Aishwarya N, Tiwari K, Tanushree P, Munesh Kumar G, Tilak R. In vitro determination of antifungal susceptibility and virulence factors in Candida species causing candidemia in North India region. Discov Public Health. 2024: 21:50. https://doi.org/10.1186/s12982-024-00175-0.
de Paula Menezes R, Silva FF, Melo SGO, Alves PGV, Brito MO, de Souza Bessa MA, et al. Characterization of Candida species isolated from the hands of the healthcare workers in the neonatal intensive care unit. Med Mycol. 2019; 57(5):588-594. https://doi.org/10.1093/mmy/myy101.
Pakshir K, Bordbar M, Zomorodian K, Nouraei H, Khodadadi H. Evaluation of CAMP-like effect, biofilm formation, and discrimination of Candida africana from vaginal Candida albicans species. J Pathog. 2017; 2017:7126258. https://doi.org/10.1155/2017/7126258.
Castrillón LE, Palma A, Padilla MC. Bio-películas fúngicas. Dermatol Rev Mex. 2013; 57 (5):350-361. Disponible en: https://www.esi.academy/wp-content/uploads/Biopeliculas_fungicas.pdf
Morales-López S, Ustate K, Pedrozo Z, Torres Y. Tipificación bioquímica y evaluación de la patogenicidad de aislamientos vulvovaginales del complejo Candida albicans. Biomed. 2023; 43(1):194-205. https://doi.org/10.7705/biomedica.6861.
López-Ávila K, Dzul-Rosado KR, Lugo- Caballero C, Arias-León JJ, Zavala-Castro JE. Mecanismos de resistencia antifúngica de los azoles en Candida albicans. Una revisión. Rev Biomédica. 2016; 27(3):127-136. https://doi.org/10.32776/revbiomed. v27i3.541.
Siddiqui R, Mendiratta D, Siddiqui A, Rukadikar A. A study of the association between virulence factors and antifungal susceptibility profile of Candida species recovered from cases of vulvovaginal candidiasis. J Family Med Prim Care. 2023; 12(1):152-159. https://doi.org/10.4103/jfmpc.jfmpc_1479_22.
Berkow E, Lockhart S. Fluconazole resistance in Candida species: a current perspective. Infect Drug Resist. 2017; 10:237-245. https://doi.org/10.2147/idr.s118892.
Tapia C. Candidiasis vulvovaginal. Rev Chil Infectol. 2008; 25(4):312. https://doi.org/10.4067/S0716-1018200800040 0016.
Makanjuola O, Bongomin F, Fayemiwo SA. An update on the roles of non-albicans Candida species in vulvovaginitis. J Fungi (Basel). 2018; 4(4):121. https://doi.org/10.3390/jof4040121
Quindós G, Cantón E, Espinel A, López J, Pemán F, Mazuelos E, et al. Resistencia a los fármacos antifúngicos. En: Quindós G. Micología Clínica. 1era ed. Elsevier; Barcelona, España: 2015. p 265-278. Disponible en: https://books.google.co.ve/books?id=MuJiCAAAQBAJ&printsec=frontcover&hl=es#v=onepage&q&f=false
Leite-Jr DP, Vivi-Oliveira VK, Maia MLS, Macioni MB, Oliboni GM, de Oliveira, et al. The Candida Genus complex: biology, evolution, pathogenicity and virulence, beyond the Candida albicans paradigm. A comprehensive review. Virol Immunol J. 2023; 7(2):000331. https://doi.org/10.23880/vij-16000331.
Willems HME, Ahmed SS, Liu J, Xu Z, Peters BM. Vulvovaginal candidiasis: A current understanding and burning questions. J Fungi (Basel). 2020; 6(1):27. https://doi.org/10.3390/jof6010027.
Arenas Guzmán R. Candidosis (Candidiasis). En: Arenas Guzmán R, editor. Micología Médica Ilustrada. 5a ed. México: McGraw-Hill; 2014. p. 242-248. Disponible en: https://biblioteca-digital-cefamus.we-bnode.mx/micologia-medica2/
Life Worldwide. Mucosal Candida. Fungal Education. 2019 [citado el 28 de diciembre de 2024]. Disponible en: https://en.fungaleducation.org/mucosal-candida/.
Miró MS, Rodríguez E, Vigezzi C, Icely PA, Gonzaga de Freitas Araújo M, Riera FO, et al. Candidiasis vulvovaginal: una antigua enfermedad con nuevos desafíos. Rev Iberoam Micol. 2017; 34(2):65-71. https://doi.org/10.1016/j.riam.2016.11.006.
Mohammadi F, Ghasemi Z, Familsatarian B, Salehi E, Sharifynia S, Barikani A, et al. Relationship between antifungal susceptibility profile and virulence factors in Candida albicans isolated from nail specimens. Rev Soc Bras Med Trop. 2020; 53: e20190214. https://doi.org/10.1590/0037-8682-0214-2019.
Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clin Microbiol Rev. 2010; 23(2):253-273. https://doi.org/10.1128/cmr.00076-09.
Cassone A. Vulvovaginal Candida albicans infections: pathogenesis, immunity and vaccine prospects. BJOG. 2015; 122(6):785-794. https://doi.org/10.1111/1471-0528.12994.
Sobel JD, Sobel R. Current treatment options for vulvovaginal candidiasis caused by azole-resistant Candida species. Expert Opin Pharmacother. 2018; 19(9):971-977. https://doi.org/10.1080/14656566.2018.1476490.
Sriphannam C, Nuanmuang N, Saengsawang K, Amornthipayawong D, Kummasook A. Anti-fungal susceptibility and virulence factors of Candida spp. isolated from blood cultures. J Mycol Med. 2019; 29(4):325-330. https://doi.org/10.1016/j.mycmed.2019.08.001.
Lamoth F, Lockhart SR, Berkow EL, Calandra T. Changes in the epidemiological landscape of invasive candidiasis. J Anti-microb Chemother. 2018; 73(1):i4-i13. https://doi.org/10.1093/jac/dkx444.
Panizo MM, Reviákina V, Flores Y, Montes W, González G. Actividad de fosfolipasas y proteasas en aislados clínicos de Candida spp. Rev Soc Ven Microbiol. 2005; 25(2):64-71. Disponible en: https://ve.scielo.org/scielo.php?pid=S1315-25562005000200006&script=sci_arttext.
Castellani A. Further researches on the long viability and growth of many pathogenic fungi and some bacteria in sterile distilled water. Mycopathol Mycol Appl. 1963; 20:1-6. https://doi.org/10.1007/bf02054872.
Echeverría A, Durante AG, Arechavala A, Negroni R. Estudio comparativo de dos medios de cultivo para la detección de la actividad de fosfolipasa en cepas de Candida albicans y Cryptococcus neoformans. Rev Iberoam Micol. 2002; 19:95-98. Disponible en: https://reviberoammicol.com/2002-19/095098.pdf.
Price MF, Wilkinson ID, Gentry LO. Plate method for detection of phospholipase activity in Candida albicans. Sabouraudia. 1982; 20(1):7-14. https://doi.org/10.1080/00362178285380031.
Aoki S, Ito-Kuwa S, Nakamura Y, Masuhara T. Comparative pathogenicity of wild-type strains and respiratory mutants of Candida albicans in mice. Zentralbl Bakteriol. 1990; 273:332-343. https://doi.org/10.1016/S0934-8840(11)80437-8.
Cruz Choappa R, Vieille Oyarzo P. Nuevos nombres para antiguas especies fúngicas de importancia médica. Rev Chil Infectol. 2023; 40(5): 461-464. http://doi.org/10.4067/s0716-10182023000500461.
De Melo Riceto ÉB, de Paula Menezes R, Penatti MPA, dos Santos Pedroso R. Enzymatic and hemolytic activity in different Candida species. Rev Iberoam Micol. 2015; 32(2):79-82. https://doi.org/10.1016/j.riam.2013.11.003.:79-82.
Ortolan Rörig KC, Colacite J, Abegg MA. Produção de fatores de virulência in vitro por espécies patogênicas do gênero Candida. Rev Soc Bras Med Trop. 2009; 42(2):225-227. https://doi.org/10.1590/S0037-86822009000200029.
de Paula Menezes R, de Melo Riceto ÉB, Borges AS, de Brito Roder DV, dos Santos Pedroso R. Evaluation of virulence factors of Candida albicans isolated from HIV-positive individuals using HAART. Arch Oral Biol. 2016; 66:61-65. https://doi.org/10.1016/j.archoralbio.2016.02.004.
Moreno X, Ventura M, Panizo MM, Garcés MF. Evaluación de la formación de biopelículas en aislamientos bacterianos y fúngicos por el método semicuantitativo de microtitulación con cristal violeta y el cualitativo de agar con rojo Congo. Biomédica. 2023; 43(Suppl 1):77-88. https://doi.org/10.7705/biomedica.6732.
Stepanovic S, Vukovic D, Dakic I, Savic B, Svabic-Vlahovic M. A modified micro-titer-plate test for quantification of staphylococcal biofilm formation. J Microbiol Methods. 2000; 40(2):175-179. https://doi.org/10.1016/s0167-7012(00)00122-6.
Ochiuzzi ME, Arechavala A, Guelfand L, Maldonado I, Soloaga R, Red de Micología CABA, Argentina. Evaluación de las tarjetas AST-YSO1 del sistema Vitek 2 para determinar la sensibilidad a antifúngicos de levaduras del género Candida. Rev Argent Microbiol. 2014; 46(2):111-118. https://doi.org/10.1016/S0325-7541(14)70058-6.
Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antifungal Susceptibility Testing of Yeasts. 2nd ed. CLSI Supplement M60- Ed 2. Wayne, PA: Clinical and Laboratory Standards Institute; 2020. Disponible en: https://www.clsi.org.
Pfaller MA, Espinel-Ingroff A, Canton E, Castanheira M, Cuenca-Estrella M, Diekema DJ, et al. Wild-type MIC distributions and epidemiological cutoff values for amphotericin B, flucytosine, and itraconazole and Candida spp. as determined by CLSI broth microdilution. J Clin Micro-biol. 2012; 50(6):2040-2046. https://doi.org/10.1128/JCM.00248-12.
Hube B. From commensal to pathogen: stage and tissue-specific gene expression of Candida albicans. Curr Opin Microbiol. 2004;7(4):336–341. https://doi.org/10.1016/j.mib.2004.06.003.
Jacobsen ID. The role of host and fungal factors in the commensal-to-pathogen transition of Candida albicans. Curr Clin Microbiol Rep. 2023; 10(2):55-65. https://doi.org/10.1007/s40588-023-00190-w.
Samaranayake LP, Raeside JM, Macfarlane TW. Factors affecting the phospholipase activity of Candida species in vitro. Sabouraudia. 1984; 22(3):201-207. https://doi.org/10.1080/00362178485380331.
Pandey N, Gupta MK, Tilak R. Extracellular hydrolytic enzyme activities of the different Candida spp. isolated from the blood of the intensive care unit-admitted patients. J Lab Physicians. 2018; 10(4):392-396. https://doi.org/10.4103/JLP.JLP_81_18.
Hernández-Solís SE, Rueda-Gordillo F, Rojas-Herrera RA. Actividad de la proteinasa en cepas de Candida albicans aisladas de la cavidad oral de pacientes inmunodeprimidos, con candidiasis oral y sujetos sanos. Rev Iberoam Micol. 2014; 31(2):137-140. https://doi.org/10.1016/j.riam.2013.09.003.
Tiwari P, Aishwarya N, Tiwari K, Tanushree P, Munesh Kumar G, Tilak R. In vitro determination of antifungal susceptibility and virulence factors in Candida species causing candidemia in North India region. Discov Public Health. 2024: 21:50. https://doi.org/10.1186/s12982-024-00175-0.
de Paula Menezes R, Silva FF, Melo SGO, Alves PGV, Brito MO, de Souza Bessa MA, et al. Characterization of Candida species isolated from the hands of the healthcare workers in the neonatal intensive care unit. Med Mycol. 2019; 57(5):588-594. https://doi.org/10.1093/mmy/myy101.
Pakshir K, Bordbar M, Zomorodian K, Nouraei H, Khodadadi H. Evaluation of CAMP-like effect, biofilm formation, and discrimination of Candida africana from vaginal Candida albicans species. J Pathog. 2017; 2017:7126258. https://doi.org/10.1155/2017/7126258.
Castrillón LE, Palma A, Padilla MC. Bio-películas fúngicas. Dermatol Rev Mex. 2013; 57 (5):350-361. Disponible en: https://www.esi.academy/wp-content/uploads/Biopeliculas_fungicas.pdf
Morales-López S, Ustate K, Pedrozo Z, Torres Y. Tipificación bioquímica y evaluación de la patogenicidad de aislamientos vulvovaginales del complejo Candida albicans. Biomed. 2023; 43(1):194-205. https://doi.org/10.7705/biomedica.6861.
López-Ávila K, Dzul-Rosado KR, Lugo- Caballero C, Arias-León JJ, Zavala-Castro JE. Mecanismos de resistencia antifúngica de los azoles en Candida albicans. Una revisión. Rev Biomédica. 2016; 27(3):127-136. https://doi.org/10.32776/revbiomed. v27i3.541.
Siddiqui R, Mendiratta D, Siddiqui A, Rukadikar A. A study of the association between virulence factors and antifungal susceptibility profile of Candida species recovered from cases of vulvovaginal candidiasis. J Family Med Prim Care. 2023; 12(1):152-159. https://doi.org/10.4103/jfmpc.jfmpc_1479_22.
Berkow E, Lockhart S. Fluconazole resistance in Candida species: a current perspective. Infect Drug Resist. 2017; 10:237-245. https://doi.org/10.2147/idr.s118892.
Tapia C. Candidiasis vulvovaginal. Rev Chil Infectol. 2008; 25(4):312. https://doi.org/10.4067/S0716-1018200800040 0016.
Makanjuola O, Bongomin F, Fayemiwo SA. An update on the roles of non-albicans Candida species in vulvovaginitis. J Fungi (Basel). 2018; 4(4):121. https://doi.org/10.3390/jof4040121
Quindós G, Cantón E, Espinel A, López J, Pemán F, Mazuelos E, et al. Resistencia a los fármacos antifúngicos. En: Quindós G. Micología Clínica. 1era ed. Elsevier; Barcelona, España: 2015. p 265-278. Disponible en: https://books.google.co.ve/books?id=MuJiCAAAQBAJ&printsec=frontcover&hl=es#v=onepage&q&f=false
Published
2026-03-04
How to Cite
Moreno-Calderón, X., Cantero-Alvarado, A., Vivas-Parababire, M. G., & Panizo-Domínguez, M. M. (2026). Factores de virulencia y su efecto sobre la sensibilidad a los fármacos antifúngicos de Candida albicans causante de vulvovaginitis candidiásica recurrente.: Virulence factors and their effect on antifungal sensitivity of Candida albicans causing recurrent vulvovaginal candidiasis. Investigación Clínica, 67(1), 45-56. https://doi.org/10.54817/IC.v67n1a04
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