Does alternation of Candida albicans TUP1 gene expression affect the progress of symptomatic recurrent vulvovaginal candidiasis?

Document Type : Original Articles

Authors

1 Department of Medical Mycology, Faculty of Medical Sciences, Iran University of Medical Sciences, Tehran, Iran

2 Invasive Fungi Research Centre,Communicable Diseases Institute / Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

3 Student Research Committee , Mazandaran University of Medical Sciences, Sari, Iran

4 Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Community Medicine, Faculty of Medical Sciences, Iran University of Medical Sciences, Tehran, Iran

6 Department of Microbiology, Faculty of Medical Sciences, Iran University of Medical Sciences, Tehran, Iran

7 Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Background and Purpose: Recurrent vulvovaginal candidiasis (RVVC) is one of the most common gynecological conditions in healthy and diabetic women, as well as antibiotic users. The present study was conducted to determine the relationship between TUP1 gene expression patterns and symptomatic recurrent C. albicans infections.
Materials and Methods: This research was performed on C. albicans samples isolated from the vaginal specimens obtained from 31 individuals with RVVC in 2016. The reference strain C. albicans ATCC 10231, 10 C. albicans strains isolated from minimally symptomatic patients, and 10 isolates from asymptomatic patients were also used as control strains. The relative mRNA expression of the TUP1 gene was quantified using quantitative real-time polymerase chain reaction (QRT-PCR).
Results: The QRT-PCR results revealed that TUP1 mRNA expression was significantly decreased (0.001-0.930 fold) in the C. albicans isolates obtained from RVVC patients (p <0.001). However, no TUP1 expression was detectable in the isolates collected from asymptomatic patients. The results also indicated a significant correlation between TUP1 mRNA expression level and the severity of itching and discharge (p <0.001).
Conclusion: The present results were suggestive of the probable contribution of TUP1, as a part of the transcriptional repressor, to the severity of the symptoms related to C. albicans infections in the vagina. Regarding this, it is required to perform more in vivo studies using a larger sample size to characterize the regulatory or stimulatory function of TUP1 in the severity of RVVC symptoms. Furthermore, the study and identification of the genes involved in the severity of the symptomatic manifestations of C. albicans, especially in resistant strains, may lead to the recognition of an alternative antifungal target to enable the development of an effective agent.

Keywords


1. Adib SM, Bared EE, Fanous R, Kyriacos S. Practices of Lebanese gynecologists regarding treatment of recurrent vulvovaginal candidiasis. N Am J Med Sci. 2011; 3(9):406-10.
2. Lema VM. Recurrent vulvo-vaginal candidiasis: diagnostic and management challenges in a developing country context. Obstet Gynecol Int J. 2017; 7(5):260. 
3. Ghazanfari M, Falahati M, Fattahi A, Bazrafshan F, Nami S, Hosseinzadeh M, et al. Is MBL serum concentration a reliable predictor for recurrent vulvovaginal candidiasis? Mycoses. 2017; 62(2):106-11.
4. Bernstein JA, Seidu L. Chronic vulvovaginal Candida hypersensitivity: an underrecognized and undertreated disorder by allergists. Allergy Rhinol. 2015; 6(1):44-9.
5. Rosentul DC, Delsing CE, Jaeger M, Plantinga TS, Oosting M, Costantini I, et al. Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis. Front Microbiol. 2014; 5:483.
6. Aguin TJ, Sobel JD. Vulvovaginal candidiasis in pregnancy. Curr Infect Dis Rep. 2015; 17(6):462.
7. Gonçalves B, Ferreira C, Alves CT, Henriques M, Azeredo J, Silva S. Vulvovaginal candidiasis: epidemiology, microbiology and risk factors. Crit Rev Microbiol. 2016; 42(6):905-27.
8. Whaley SG, Berkow EL, Rybak JM, Nishimoto AT, Barker KS, Rogers PD. Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species. Front Microbiol. 2017; 12:2173.
9. Gunther LS, Martins HP, Gimenes F, Abreu AL, Consolaro ME, Svidzinski T. Prevalence of Candida albicans and non-albicans isolates from vaginal secretions: comparative evaluation of colonization, vaginal candidiasis and recurrent vaginal candidiasis in diabetic and non-diabetic women. Sao Paulo Med J. 2014; 132(2):116-20.
10. Kadosh D, Johnson AD. Induction of the Candida albicans filamentous growth program by relief of transcriptional repression: a genome-wide analysis. Mole Boil Cell. 2005; 16(6):2903-12.
11. Saville SP, Lazzell AL, Monteagudo C, Lopez-Ribot JL.
Engineered control of cell morphology in vivo reveals distinct roles for yeast and filamentous forms of Candida albicans during infection. Eukaryoti Cell. 2003; 2(5):1053-60.
12. Brown AJ. Morphogenetic signaling pathways in Candida albicans. In: Calderone R, editor. Candida and candidiasis. Washington, DC: ASM Press; 2002. P. 95-106.
13. Calderone R, Gow NA. Host recognition by Candida species. In: Calderone R, editor. Candida and candidiasis. Washington, DC: ASM Press; 2002. P. 67-86. 
14. Romani L, Bistoni F, Puccetti P. Adaptation of Candida albicans to the host environment: the role of morphogenesis in virulence and survival in mammalian hosts. Curr Opin Microbiol. 2003; 6(4):338-43. 
15. Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clin Microbiol Rev. 2010; 23(2):253-73. 
16. Thompson DS, Carlisle PL, Kadosh D. Coevolution of morphology and virulence in Candida species. Eukaryot Cell. 2011; 10(9):1173-82. 
17. Sudbery PE. Growth of Candida albicans hyphae. Nat Rev Microbial. 2011; 9(10):737-48. 
18. Lane S, Birse C, Zhou S, Matson R, Liu H. DNA array studies demonstrate convergent regulation of virulence factors by Cph1, Cph2, and Efg1 in Candida albicans. J Biol Chem. 2001; 276(52):48988-96. 
19. Felk A, Kretschmar M, Albrecht A, Schaller M, Beinhauer S, Nichterlein T, et al. Candida albicans hyphal formation and the expression of the Efg1-regulated proteinases Sap4 to Sap6 are required for the invasion of parenchymal organs. Infect Immune. 2002; 70(7):3689-700. 
20. Braun BR, Johnson AD. TUP1, CPH1 and EFG1 make independent contributions to filamentation in Candida albicans. Genet. 2000; 155(1):57-67. 
21. Brand A. Hyphal growth in human fungal pathogens and its role in virulence. Int J Microbiol. 2011; 2012:517529.
22. Jackson BE, Mitchell BM, Wilhelmus KR. Corneal virulence of Candida albicans strains deficient in Tup1-regulated genes. Invest Ophthalmol Vis Sci. 2007; 48(6):2535-9. 
23. Braun BR, Head WS, Wang MX, Johnson AD. Identification and characterization of TUP1-regulated genes in Candida albicans. Genet. 2000; 156(1):31-44. 
24. Kebaara BW, Langford ML, Navarathna DH, Dumitru R, Nickerson KW, Atkin AL. Candida albicans Tup1 is involved in farnesol-mediated inhibition of filamentous-growth induction. Eukaryot Cell. 2008; 7(6):980-7. 
25. Fleischmann J, Rocha MA. Decrease in ribosomal RNA in Candida albicans induced by serum exposure. PLoS One. 2015; 10(5):e0124430. 
26. Kim D, Shin WS, Lee KH, Young Park J, Koh CM. Rapid differentiation of Candida albicans from other Candida species using its unique germ tube formation at 39 C. Yeast. 2002; 19(11):957-62. 
27. Fattahi A, Zaini F, Kordbacheh P, Rezaie S, Safara M, Fateh R, et al. Evaluation of mRNA expression levels of cyp51a and mdr1, candidate genes for voriconazole resistance in Aspergillus flavus. Jundishapur J Microbiol. 2015; 8(12):e26990.