Volume 6, Issue 3 (July 2020)                   RABMS 2020, 6(3): 153-159 | Back to browse issues page


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Diba K, Khademvatan S, Jaafari K, Abharian S. Characterization of ERG11 Gene in Drug-Resistant Candida Albicans Isolated from Iranian Cases of Recurrent Vulvovaginal Candidiasis. RABMS. 2020; 6 (3) :153-159
URL: http://ijrabms.umsu.ac.ir/article-1-116-en.html
Associate Professor in Medical Mycology, Molecular and Cellular Research Center, Urmia University of Medical Sciences, Urmia, Iran , diba.k@umsu.ac.ir
Abstract:   (997 Views)
Background & Aims:  Candida albicans is the most common fungal pathogen of human infections. C. albicans is responsible for significant mucosal infections such as vulvovaginitis in women. Azoles inhibit the cytochrome P450 14α-lanosterol demethylase, as a part of the ergosterol biosynthetic pathway is encoded by the ERG11 gene. Some mutations in ERG 11 could cause resistance to azole drugs.  Detection of the mutations of the gene in the present study helped us to explain drug resistances in some vaginal isolates of C. albicans and other Candida species.
Materials & Methods: A multicenter, experimental study was conducted at Cellular and Molecular Research Center and Kowsar Gynecology Center affiliated to UMSU from October 2016 to July 2017. Women with symptomatic vaginitis (20-45 years old) were asked to take part in the study. 192 women allowed vaginal swabs to be obtained. For the identifications, culture on SGA4% and CHROM agar Candida were conducted followed by PCR-RFLP. A disc diffusion method was performed based on the standard guideline of the National Committee for Clinical Laboratory Standards (NCCLS) to determine level of susceptibility against fluconazole and clotrimazole (most current use for the treatment of VVC). DNA extraction and PCR amplification of the ERG11 gene were performed.
Results: As we showed in the Table (1), 69.1% of all Candida isolates carried the ERG11 gene. It was detected in 49(68.1%), 5 (55.6%), and 7(77.8%) cases of C. albicans, C. krusei, and C. glabrata, respectively.  Among the C. albicans isolates resistant to Clotrimazole, 8(53.3%) had ERG11 gene while 7(46.7%) did not. Among all the C. glabrata isolates resistant to Clotrimazole, 40% carried ERG11 while 60% did not show the gene. Also, ERG11 gene was detected in 50% of the isolated C. glabrata. ERG11 gene was observed in 53.3% of C.krusei isolates resistant to Clotrimazole and 52% of those of resistant to Fluconazole.
Conclusion: As an approximate finding, Azole resistance in the present study could be attributed to mutations in ERG11 gene
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References
1. Kim J, Sudbery P. Candida albicans, a major human fungal pathogen. J Microbiol 2011; 49(2):171-7. [DOI:10.1007/s12275-011-1064-7] [PMID]
2. Song Jl, Harry JB, Eastman RT, Oliver BG, White TC. The Candida albicans Lanosterol 14-α-demethylase (ERG11) gene promoter maximally induced after prolonged growth with antifungal drugs. Antimicrob Agents Chemother 2004; 48(4): 1136-44. [DOI:10.1128/AAC.48.4.1136-1144.2004] [PMID] [PMCID]
3. Sanglard D, Ischer F, Parkinson T, Falconer Derek, Bille J. Candida albicans Mutations in the Ergosterol Biosynthetic Pathway and Resistance to Several Antifungal Agents. Antimicrob Agents Chemother 2003 ; 47(8): 2404-12. [DOI:10.1128/AAC.47.8.2404-2412.2003] [PMID] [PMCID]
4. Akins RA. An update on antifungal targets and mechanisms of resistance in Candida albicans. Med Mycol 2005; 43: 285-318. [DOI:10.1080/13693780500138971] [PMID]
5. Henry KW, Nickels JT, Edlind TD. Upregulation of ERG Genes in Candida Species by Azoles and Other Sterol Biosynthesis Inhibitors. Antimicrob Agents Chemother 2000 ; 44(10): 2693-2700. [DOI:10.1128/AAC.44.10.2693-2700.2000] [PMID] [PMCID]
6. Sanglard D, Ischer F, Parkinson T, Falconer Derek, Bille J. Candida albicans Mutations in the Ergosterol Biosynthetic Pathway and Resistance to Several Antifungal Agents. Antimicrob Agents Chemother 2003; 47(8): 2404-12. [DOI:10.1128/AAC.47.8.2404-2412.2003] [PMID] [PMCID]
7. Sobel JD. Vulvovaginitis: when Candida becomes a problem. Dermatol Clin 1998; 16:763-8. [DOI:10.1016/S0733-8635(05)70043-7]
8. Sobel JD. Limitations of antifungal agents in the treatment of Candida vaginitis: future challenges. Drug Resist Updates 1999; 2:148-52. [DOI:10.1054/drup.1999.0088] [PMID]
9. Vazquez JA, Sobel JD, Peng G, Steele-Moore L, Schuman P, Holloway W, et al. Evolution of vaginal Candida species recovered from human immunodeficiency virus-infected women receiving fluconazole prophylaxis: the emergence of Candida glabrata? Terry Beirn Community Programs for Clinical Research in AIDS (CPCRA). Clin Infect Dis 1999; 28:1025-31. [DOI:10.1086/514746] [PMID]
10. Nguyen MH, Peacock JE Jr, Morris AJ, Tanner DC, Nguyen ML, Snydman DR, et al. The changing face of Candidemia: emergence of non-Candida albicans species and antifungal resistance. Am J Med 1996; 100: 617-23. [DOI:10.1016/S0002-9343(95)00010-0]
11. Pfaller MA, Messer SA, Hollis RJ, Jones RN, Doern GV, Brandt ME, et al. Trends in species distribution and susceptibility to fluconazole among blood stream isolates of Candida species in the United States. Diagn Microbiol Infect Dis 1999;33: 217-22. [DOI:10.1016/S0732-8893(98)00160-6]
12. Pfaller MA, Jones RN, Messer SA, Edmond MB, Wenzel RP. National surveillance of nosocomial blood stream infection due to species of Candida other than Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program. SCOPE Participant Group. Surveillance and Control of Pathogens of Epidemiologic Importance. Diagn Microbiol Infect Dis 1998; 30 (2):21-9. [DOI:10.1016/S0732-8893(97)00192-2]
13. Alexander BD, Perfect JR. Antifungal resistance trends towards the year 2000: implications for therapy and new approaches. Drugs 1997; 54:657-78. [DOI:10.2165/00003495-199754050-00002] [PMID]
14. Pfaller MA. Epidemiology of candidiasis. J Hosp Infect 1995; 30: 329-38. [DOI:10.1016/0195-6701(95)90036-5]
15. Rex JH, Rinaldi MG, Pfaller MA. Resistance of Candida species to fluconazole. Antimicrob Agents Chemother 1995;39: 1-8. [DOI:10.1128/AAC.39.1.1] [PMID] [PMCID]
16. Marr KA, Lyons CN, Rustad TR, Bowden RA, White TC, Rustad T. Rapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR. Antimicrob Agents Chemother 1998; 42:2584-9. [DOI:10.1128/AAC.42.10.2584] [PMID] [PMCID]
17. Sanglard D, Kuchler K, Ischer F, Pagani JL, Monod M, Bille J. Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters. Antimicrob Agents Chemother 1995; 39:2378-86. [DOI:10.1128/AAC.39.11.2378] [PMID] [PMCID]
18. Sanglard D, Ischer F, Koymans L, Bille J. Amino acid substitutions in the cytochrome P-450 lanosterol 14alpha-demethylase (CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents. Antimicrob Agents Chemother 1998; 42:241-53. [DOI:10.1128/AAC.42.2.241] [PMID] [PMCID]
19. Arias A, Arevalo MP, Andreu A, Rodriguez C, Sierra A. Candida glabrata: in vitro susceptibility of 84 isolates to eight antifungal agents. Chemotherapy 1996; 42:107-11. [DOI:10.1159/000239429] [PMID]
20. Cross EW, Park S, Perlin DS. Cross-resistance of clinical isolates of Candida albicans and Candida glabrata to over-the-counter azoles used in the treatment of vaginitis. Microb Drug Resist 2000; 6:155-6. [DOI:10.1089/107662900419474] [PMID]
21. Mirhendi H, Makimura K, Khoramizadeh MA. One-enzyme PCR-RFLP assay for identification of six medically importnat Candida species. Jpn Med Mycol 2006; 47: 225-9. [DOI:10.3314/jjmm.47.225] [PMID]
22. Mirhendi H, Diba K, Rezaaey A, Jalalizand N. Colony-PCR is a rapid and sensitive method for DNA amplification in yeasts. Iran J Public Health 2007; 1: 40-4. [google scholar]
23. National Committee for Clinical Laboratory Standards (NCCLS). Reference method for broth dilution antifungal susceptibility testing of yeasts: approved standard. NCCLS document M27-A Wayne, PA: NCCLS; 1997.
24. Eifeky DS, Gohar NM, El-Seidi EA, Ezzat MM, Aboelew SH. Species identification and antifungal susceptibility pattern of Candida isolates in cases of vulvovaginal candidiasis. Alex j med 2016;52(3):269-77. [DOI:10.1016/j.ajme.2015.10.001]
25. Salehi Z, Seifi Z, Zarei A. sensitivity of vaginal isolates of Candida to eight antifungal drugs isolated from Ahwaz, Iran. Jundishapour J Microbiol 2012; 5(4): 574-7. [DOI:10.5812/jjm.4556]
26. Al-mamari A, Al-buryhi M, Al-heggami A, Al-hag S. Identify and sensitivity to antifungal drugs of Candida species causing vaginitis isolated from vulvovaginal infected patient in Sana'a. Der Pharma Chemica 2014; 6(1): 336-42. [ResearchGate]
27. Khan F, Baqai R. Invitro antifungal sensitivity of Fluconazole, Clotrimazole and Nystatin against vaginal candidiasis in females of childbearing age. J Ayub Med Coll Abbottabad 2010; 22(4):197-200. [google scholar]
28. Richter SS, Galask RP, Messer SA, Hillis RJ, Diekema DJ, Pfaller MA. Antifungal Susceptibility of Candida species causing vulvovaginitis and epidemiology of recurrent cases. J Clin Microbiol 2005;43(5):2155-62. [DOI:10.1128/JCM.43.5.2155-2162.2005] [PMID] [PMCID]
29. Fakhari E, Nakhoda A, Emami M. Antifungal susceptibilities of Candida species causing vulvuvaginal by disk diffusion. Jundishapour J Microbiol 2013; special edit, p7.
30. Lee MK, Williams LE, Warnock DW, Arthington BA. Drug resistance genes trailing growth in Candida albicans isolates. J Antimicrobiol chemother 2004; 53: 217-24. [DOI:10.1093/jac/dkh040] [PMID]
31. Kakeya H, Miyazaki T, Miyazaki Y, Kohno S. Azole resistance in Candida spp. Med Mycol 2003; 44(2):87-92. [DOI:10.3314/jjmm.44.87] [PMID]
32. Sanglard D, Ischer F, Parkinson T, Falconer D, Bille J. Candida albicans Mutations in the Ergosterol Biosynthetic Pathway and Resistance to Several Antifungal Agents. Antimicrob Agents Chemother 2003; 47(8): 2404-12. [DOI:10.1128/AAC.47.8.2404-2412.2003] [PMID] [PMCID]
33. Gandhi TN, Patel MG, Jain MR. antifungal susceptibility of Candida against six antifungal drugs by disc diffusion method isolated from vulvovaginal candididasis. Int J Res Rev 2015; 7(11):20. [address]
34. Lee MK, Williams LE, Warnock DW, Arthington BA. Drug resistance genes trailing growth in Candida albicans isolates. J Antimicrobiol chemother 2004; 53: 217-24. [DOI:10.1093/jac/dkh040] [PMID]

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