Prevalence, molecular identification, and genotyping of Candida species recovered from oral cavity among patients with diabetes mellitus from Tehran, Iran

Document Type : Original Article


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

2 Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

3 Department of General Microbiology, Microbiology Institute, Federal University of Rio de Janeiro, Brazil

4 Infectious Disease Research Center, Birjand University of Medical Sciences, Birjand, Iran

5 Department of Medical Parasitology and Mycology, Infectious Diseases and Tropical Medicine Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran


Background: Oral candidiasis (OC) has been noticed as a common mucous membrane infection in immunocompromised patients such as that diabetes. This study, focused on the genotyping of Candida albicans and enzymatic activities of Candida species recovered from oral mucosa among diabetes patients and healthy individuals. Materials and Methods: Specimens were obtained from oral mucosa of One-hundred and sixty patients with type 2 diabetic and 108 healthy individuals. All isolates were definitely identified by ribosomal DNA (rDNA) gene sequencinghHydrophobicity, hemolytic activities of Candida species and genotypes of C. albicans were determined through polymerase chain reaction (CA-INT). Results:, Eighty eight (55%) samples out of 160, were positive for Candida species in diabetic patients. Moreover, 79.5% (70/88) and 20.5% (18/88) isolates belonged to the C. albicans and non-albicans Candida species respectively. Three genotypes of C. albicans have recovered in diabetic patients: genotype A (71.42%), B (21.42%), and C (7.14%). In healthy individuals, 42.6% (46/102) Candida species recovered from oral cavity, with the highest prevalence of genotype A (76.6% of C. albicans). Additionally, hydrophobicity and hemolytic activities from Candida species were significantly greater in diabetes patients than healthy nondiabetic subjects. Conclusion: Collectively, C. albicans was the most causative agent isolated from diabetes patients and non-diabetes healthy individuals. Genotype A, as the most remarkable genotype, should be mentioned in both groups. Higher potential hydrophobicity and hemolytic activities of Candida species in diabetic patients compared to healthy cases suggest these features triggering pathogenicity of OC in diabetes patients.


Fanello S, Bouchara J, Sauteron M, Delbos V, Parot E, et al. Predictive value of oral colonization by Candida yeasts for the onset of a nosocomial infection in elderly hospitalized patients. J Med Microbiol 2006;55:223-8.  Back to cited text no. 1
Rodrigues CF, Rodrigues ME, Henriques M. Candida sp. infections in patients with diabetes mellitus. J Clin Med 2019;8:76.  Back to cited text no. 2
Maheshwari M, Kaur R, Chadha S. Candida species prevalence profile in HIV seropositive patients from a major tertiary care hospital in New Delhi, India. J Pathog 2016;2016:6204804.  Back to cited text no. 3
Perlroth J, Choi B, Spellberg B. Nosocomial fungal infections: Epidemiology, diagnosis, and treatment. Med Mycol 2007;45:321-46.  Back to cited text no. 4
Willis A, Coulter W, Fulton C, Hayes J, Bell P, et al. Oral candidal carriage and infection in insulin-treated diabetic patients. Diabetic Med 1999;16:675-9.  Back to cited text no. 5
Karaa A, Goldstein A. The spectrum of clinical presentation, diagnosis, and management of mitochondrial forms of diabetes. Pediatr Diabetes 2015;16:1-9.  Back to cited text no. 6
King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: Prevalence, numerical estimates, and projections. Diabetes Care 1998;21:1414-31.  Back to cited text no. 7
Esteghamati A, Larijani B, Aghajani MH, Ghaemi F, Kermanchi J, Shahrami A, et al. Diabetes in Iran: Prospective analysis from first nationwide diabetes report of national program for prevention and control of diabetes (NPPCD-2016). Sci Rep 2017;17:13461.  Back to cited text no. 8
Kumar B, Padshetty N, Bai KY, Rao M. Prevalence of Candida in the oral cavity of diabetic subjects. J Assoc Phys India 2005;53:599.  Back to cited text no. 9
Javed F, Ahmed HB, Mehmood A, Saeed A, Al-Hezaimi K, et al. Association between glycemic status and oral Candida carriage in patients with prediabetes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2014;117:53-8.  Back to cited text no. 10
Rodrigues CF, Henriques. Oral mucositis caused by Candida glabrata biofilms: Failure of the concomitant use of fluconazole and ascorbic acid. Ther Adv Infect Dis 2017;4:10-7.  Back to cited text no. 11
Darwazeh A, MacFarlane TW, McCuish A, Lamey PJ. Mixed salivary glucose levels and candidal carriage in patients with diabetes mellitus. J Oral Maxillofac Pathol 1991;20:280-3.  Back to cited text no. 12
Naik R, Ahmed Mujib B, Raaju U, Telagi N. Assessing oral candidal carriage with mixed salivary glucose levels as non-invasive diagnostic tool in type-2 diabetics of Davangere, Karnataka, India. J Clin Diagn Res 2014;8:ZC69-72.  Back to cited text no. 13
Sashikumar R, Kannan R. Salivary glucose levels and oral candidal carriage in type II diabetics. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:706-11.  Back to cited text no. 14
Balan P, Gogineni SB, Kumari S, Shetty V, Rangare AL, et alCandida carriage rate and growth characteristics of saliva in diabetes mellitus patients: A case-control study. J Dent Res Dent Clin Dent Prospects 2015;9:274-9.  Back to cited text no. 15
Malic S, Hill KE, Ralphs JR, Hayes A, Thomas DW, et al. Characterization of Candida albicans infection of an in vitro oral epithelial model using confocal laser scanning microscopy. Oral Microbiol Immunol 2007;22:188-94.  Back to cited text no. 16
Martorano-Fernandes L, Dornelas-Figueira LM, Marcello-Machado RM, Silva RB, Magno MB. Oral candidiasis and denture stomatitis in diabetic patients: Systematic review and meta-analysis. Braz Oral Res 2020;34:e113.  Back to cited text no. 17
van der Meer JW, van de Veerdonk FL, Joosten LA, Kullberg BJ, Netea MG. Severe Candida spp. infections: New insights into natural immunity. Int J Antimicrob Agents 2010;36:S58-62.  Back to cited text no. 18
Zahir R, HimratulAznita WH. Distribution of Candida in the oral cavity and its differentiation based on the internally transcribed spacer (ITS) regions of rDNA. Yeast 2013;30:13-23.  Back to cited text no. 19
Barros LM, Boriollo MF, Alves AC, Klein MI, Gonçalves RB, et al. Genetic diversity and exoenzyme activities of Candida albicans and Candida dubliniensis isolated from the oral cavity of Brazilian periodontal patients. Arch Oral Biol 2008;53:1172-8.  Back to cited text no. 20
Bujdáková H, Didiášová M, Drahovská H, Černáková L. Role of cell surface hydrophobicity in Candida albicans biofilm. Open Life Sci 2013;8:259-62.  Back to cited text no. 21
Singleton DR, Masuoka J, Hazen KC. Surface hydrophobicity changes of two Candida albicans serotype B mnn4delta mutants. Eukaryot Cell 2005;4:639-48.  Back to cited text no. 22
Deorukhkar SC, Saini S, Mathew S. Virulence factors contributing to pathogenicity of Candida tropicalis and its antifungal susceptibility profile. Int J Microbiol Res 2014;2014:456878.  Back to cited text no. 23
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;32:79-82.  Back to cited text no. 24
Fatahinia M, Poormohamadi F, Mahmoudabadi AZ. Comparative study of esterase and hemolytic activities in clinically important Candida species, isolated from oral cavity of diabetic and non-diabetic individuals. Jundishapur J Microbiol 2015;8:e20893.  Back to cited text no. 25
Chen KW, Chen YC, Lo HJ, Odds FC, Wang TH, et al. Multilocus sequence typing for analyses of clonality of Candida albicans strains in Taiwan. J Clin Microbiol 2006;44:2172-8.  Back to cited text no. 26
Colombo AL, Guimarães T, Camargo LF, Richtmann R, Queiroz-Telles FD, et al. Brazilian guidelines for the management of candidiasis-a joint meeting report of three medical societies: Sociedade Brasileira de Infectologia, Sociedade Paulista de Infectologia and Sociedade Brasileira de Medicina Tropical. Braz J Infect Dis 2013;17:283-312.  Back to cited text no. 27
Odds FC, Jacobsen MD. Multilocus sequence typing of pathogenic Candida species. Eukaryot Cell 2008;7:1075-84.  Back to cited text no. 28
Sardi JC, Duque C, Höfling JF, Gonçalves RB. Genetic and phenotypic evaluation of Candida albicans strains isolated from subgingival biofilm of diabetic patients with chronic periodontitis. Sabouraudia 2012;50:467-75.  Back to cited text no. 29
Song X, Eribe ER, Sun J, Hansen BF, Olsen I. Genetic relatedness of oral yeasts within and between patients with marginal periodontitis and subjects with oral health. J Periodent Res 2005;40:446-52.  Back to cited text no. 30
Kamali M, Sarvtin MT, Parsanasab H. Prevalence of Candida infection in patients with Type 2 diabetes mellitus in Sari, North of Iran. Biomed Pharmacol J 2016;9:731-4.  Back to cited text no. 31
Falahati M, Farahyar S, Akhlaghi L, Mahmoudi S, Sabzian K, et al. Characterization and identification of candiduria due to Candida species in diabetic patients. Curr Med Mycol 2016;2:10-4.  Back to cited text no. 32
Zomorodian K, Kavoosi F, Pishdad G, Mehriar P, Ebrahimi H, et al. Prevalence of oral Candida colonization in patients with diabetes mellitus. J Mycol Med 2016;26:103-10.  Back to cited text no. 33
Khedri S, Santos A, Roudbary M, Hadighi R, Falahati M, et al. Iranian HIV/AIDS patients with oropharyngeal candidiasis: Identification, prevalence and antifungal susceptibility of Candida species. Lett Appl Microbiol 2018;67:392-9.  Back to cited text no. 34
Roudbary M, Roudbarmohammadi S, Bakhshi B, Farhadi Z, Nikoomanesh F. Identification of Candida species isolated from Iranian women with vaginal candidiasis by PCR-RFLP method. Eur J Exp Biol 2013;3:365-9.  Back to cited text no. 35
Bii C, Kangogo M, Revathi G, Wanyoike M. Genotypes of Candida albicans from clinical sources in Nairobi Kenya. Afr J Microbiol Res 2009;3:475-7.  Back to cited text no. 36
Tang HJ, Liu WL, Lin HL, Lai CC. Epidemiology and prognostic factors of candidemia in elderly patients. Geriatr Gerontol Int 2015;15:688-93.  Back to cited text no. 37
Hammad MM, Darwazeh AM, Idrees MM. The effect of glycemic control on Candida colonization of the tongue and the subgingival plaque in patients with Type II diabetes and periodontitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2013;116:321-6.  Back to cited text no. 38
Rajakumari ML, Kumari PS. Prevalence of Candida species in the buccal cavity of diabetic and non-diabetic individuals in and around Pondicherry. J Mycol Med 2016;26:359-67.  Back to cited text no. 39
Silva S, Henriques M, Hayes A, Oliveira R, Azeredo J, et alCandida glabrata and Candida albicans co-infection of an in vitro oral epithelium. J Oral Maxillofac Pathol 2011;40:421-7.  Back to cited text no. 40
Rauceo JM, Gaur NK, Lee KG, Edwards JE, Klotz SA, et al. Global cell surface conformational shift mediated by a Candida albicans adhesin. Infect Immun 2004;72:4948-55.  Back to cited text no. 41
Zakikhany K, Naglik JR, Schmidt-Westhausen A, Holland G, Schaller M, et al. In vivo transcript profiling of identifies a gene essential for interepithelial dissemination. Cell Microbiol 2007;9:2938-54.  Back to cited text no. 42
Silva-Dias A, Miranda IM, Branco J, Monteiro-Soares M, Pina-Vaz C, et al. Adhesion, biofilm formation, cell surface hydrophobicity, and antifungal planktonic susceptibility: Relationship among Candida spp. Front Microbiol 2015;6:205.  Back to cited text no. 43
Nett JE, Lepak AJ, Marchillo K, Andes DR. Time course global gene expression analysis of an in vivo Candida biofilm. J Infect Dis 2009;200:307-13.  Back to cited text no. 44
Pierce CG, Vila T, Romo JA, Montelongo-Jauregui D, Wall G, et al. The Candida albicansbiofilm matrix: Composition, structure and function. J Fungi 2017;3:14.  Back to cited text no. 45
Soysa NS, Samaranayake L, Ellepola A. Diabetes mellitus as a contributory factor in oral candidosis. Diabet Med 2006;23:455-9.  Back to cited text no. 46
Tsang C, Chu F, Leung W, Jin L, Samaranayake L, et al. Phospholipase, proteinase and haemolytic activities of Candida albicans isolated from oral cavities of patients with Type 2 diabetes mellitus. J Med Microbiol 2007;56:1393-8.  Back to cited text no. 47
Silva S, Rodrigues CF, Araújo D, Rodrigues ME, Henriques M. Candida species biofilms' antifungal resistance. J Fungi 2017;3:8.  Back to cited text no. 48
Rossoni RD, Barbosa JO, Vilela SF, Jorge AO, Junqueira JC. Comparison of the hemolytic activity between C. albicans and non-albicans Candida species. Braz Oral Res 2013;27:484-9.  Back to cited text no. 49
Manfredi M, McCullough M, Al-Karaawi ZM, Hurel S, Porter S. The isolation, identification and molecular analysis of Candida spp. isolated from the oral cavities of patients with diabetes mellitus. Oral Microbiol Immunol 2002;17:181-5.  Back to cited text no. 50
Rajendran R, Robertson DP, Hodge PJ, Lappin DF, Ramage G. Hydrolytic enzyme production is associated with Candida albicans biofilm formation from patients with Type 1 diabetes. Mycopathologia 2010;170:229-35.  Back to cited text no. 51
Luo G, Samaranayake LP, Yau JY. Candida species exhibit differential in vitro hemolytic activities. J Clin Microbiol 2001;39:2971-4.  Back to cited text no. 52
de Paula Menezes R, Ferreira JC, de Sá WM, de Aquino Moreira T, Malvino LD, de Araujo LB, et al. Frequency of Candida species in a tertiary care hospital in Triangulo Mineiro, Minas Gerais State, Brazil. Rev Inst Med Trop Sao Paulo 2015;57:185-91.  Back to cited text no. 53
Imran ZK, Al-Asadi YF. Comparison of 25S and 18S primers for estimating clinical isolates of Candida diversity and evaluate their virulence in eyes infections in Iraq. Appl Sci Report 2015;9:166-71.  Back to cited text no. 54
Gong YB, Jin B, Qi H, Zhang R, Zhang XY, et al. Multilocus sequence typing of Candida albicans isolates from the oral cavities of patients undergoing haemodialysis. Sci Rep 2018;8:1-8.  Back to cited text no. 55
Kumar M, Mishra NK, Shukla PK. Sensitive and rapid polymerase chain reaction based diagnosis of mycotic keratitis through single stranded conformation polymorphism. Am J Ophthalmol 2005;140:851-7.e852.  Back to cited text no. 56
Zhao X, Oh SH, Jajko R, Diekema DJ, Pfaller MA, et al. Analysis of ALS5 and ALS6 allelic variability in a geographically diverse collection of Candida albicans isolates. Fungal Genet Biol 2007;44:1298-309.  Back to cited text no. 57