Cutaneous candidiasis in Tehran-Iran: from epidemiology to multilocus sequence types, virulence factors and antifungal susceptibility of etiologic Candida species
-
Golnar Sadeghi
,
Mina Ebrahimi-Rad
,
Masoomeh Shams-Ghahfarokhi
,
Zahra Jahanshiri
,
Esmat Mirabzadeh Ardakani
,
Ali Eslamifar
,
Seyed Fazlollah Mousavi
,
Mehdi Razzaghi-Abyaneh
Abstract
Background and Objectives: Cutaneous candidiasis is a multipicture fungal infection caused by members of the genus Candida which is considered as a public health problem all over the world with urgency of effective treatment and control. This study was performed to analyze the clinical epidemiology and molecular aspects of cutaneous candidiasis in Tehran-Iran in relation to antifungal susceptibility and virulence factors of etiologic Candida species.
Materials and Methods: Candida species were isolated from skin (27.3%) and nail scrapings (72.7%) of suspected patients and identified by ITS sequencing. Phylogeny of the isolates was evaluated using multilocus sequence typing (MLST) and antifungal susceptibility and virulence factors of the isolates were determined in relation to clinical presentation.
Results: Candida albicans was the most prevalent species (39.8%), followed by C. parapsilosis (32.9%), C. orthopsilosis (10.4%), C. tropicalis (7.9%), C. glabrata and C. guilliermondii, each (4.5%). Molecular typing of 35 C. albicans isolates by MLST revealed 28 novel sequence types with 11 singletons with 80.0% new diploid sequence types (DSTs). Majority of the isolates were susceptible to amphotericin B (91.5%), followed by posaconazole (90.3%), fluconazole (84.3%), itraconazole (74.1%), caspofungin (53.6%), and voriconazole (26.8%). Biofilm formation, yeast-to-hyphae transformation and phospholipase activity were reported species-dependent.
Conclusion: Our results demonstrated clinical epidemiology of various Candida species from cutaneous candidiasis distributed in new molecular types with increasing importance of drug resistant of non-albicans Candida species. Our results showed that drug susceptibility and genetic variability of Candida species may be attributed to their clinical features and source of isolation.
1. Kühbacher A, Burger-Kentischer A, Rupp S. Interaction of Candida Species with the Skin. Microorganisms 2017;5:E32.
2. Demiraslan H, Alabay S, Kilic AU, Borlu M, Doganay M. Cutaneous candidiasis caused by Candida glabrata in a HIV/AIDS patient. Int J STD AIDS 2013; 24:753-755.
3. Sadeghi G, Ebrahimi-Rad M, Mousavi SF, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M. Emergence of non-Candida albicans species: Epidemiology, phylogeny and fluconazole susceptibility profile. J Mycol Med 2018; 28: 51-58.
4. Amanloo S, Shams-Ghahfarokhi M, Ghahri M, Razzaghi-Abyaneh M. Genotyping of clinical isolates of Candida glabrata from Iran by multilocus sequence typing and determination of population structure and drug resistance profile. Med Mycol 2018; 56: 207-215.
5. Barchiesi F, Orsetti E, Gesuita R, Skrami E. Epidemiology, clinical characteristics, and outcome of candidemia in a tertiary referral center in Italy from 2010 to 2014. Infection 2016; 44: 205-213.
6. Fich F, Abarzúa-Araya A, Pérez M, Nauhm Y, León E. Candida parapsilosis and Candida guillermondii: Emerging pathogens in nail candidiasis. Indian J Dermatol 2014; 59: 24-29.
7. Pai V, Ganavalli A, Narayanshetty Kikkeri N. Antifungal resistance in dermatology. Indian J Dermatol 2018; 63: 361-368.
8. Dabiri M, Shams-Ghahfarokhia M, Razzaghi-Abyaneh M. Comparative analysis of proteinase, phospholipase, hydrophobicity and biofilm forming ability in Candida species isolated from clinical specimens. J Mycol Med 2018; 28: 437-442.
9. Odds FC, Jacobsen MD. Multilocus sequence typing of pathogenic Candida species. Eukaryot Cell 2008; 7: 1075-1084.
10. Su JZ, Yang YL, Rong R, Wu BQ. Genotype and homology analysis of pathogenic and colonization strains of Candida albicans from hospitalized neonates. Pediatr Neonatol 2018; 59: 488-493.
11. Bitar I, Khalaf RA, Harastani H, Tokajian S. Identification, typing, antifungal resistance profile, and biofilm formation of Candida albicans isolates from Lebanese hospital patients. Biomed Res Int 2014; 2014: 931372.
12. Tay ST, Tan HW, Na SL, Lim SL. Phenotypic and genotypic characterization of two closely related subgroups of Candida rugosa in clinical specimens. J Med Microbiol 2011; 60: 1591-1597.
13. Pfaller MA, Diekema DJ. Progress in antifungal susceptibility testing of Candida spp. by use of Clinical and Laboratory Standard Institute broth microdilution methods, 2010 to 2012. J Clin Microbiol 2012; 50: 2846-2856.
14. Clinical and Laboratory Standards Institute, Reference method for broth dilution antifungal susceptibility testing of yeasts; 4th informational supplement. CLSI document M27-S4. 2012; Wayne, PA, USA.
15. Razzaghi-Abyaneh M, Sadeghi G, Zeinali E, Alirezaee M, Shams-Ghahfarokhi M, Amani A. Species distribution and antifungal susceptibility of Candida spp. isolated from superficial candidiasis in outpatients in Iran. J Mycol Med 2014; 24(2):e43-50.
16. Zago CE, Silva S, Sanita PV, Borbugli PA, Improta Dias CM, Lordello VB. Dynamics of biofilm formation and the interaction between Candida albicans and methicillin- susceptible (MSSA) and –resistant Staphylococcus aureus (MRSA). PLoS One 2015; 10(4):e0123206.
17. Tsang CSP, Chu FCS, Leung WK, Jin LJ, Samaranayake LP, Siu SC. Phospholipase, proteinase and hemolytic activities of Candida albicans isolated from oral cavities of patients with type 2 diabetes mellitus. J Med Microbiol 2007; 56: 1393-1398.
18. Galan- Ladero MA, Blanco MT, Sacristan B, Fernandez- Calderon MC, Perez-Giraldo C, Gomez-Garcia AC. Enzymatic activities of Candida tropicalis isolated from hospitalized patients. Med Mycol 2010; 48: 207-210.
19. Negri M, Martins M, Henriques M, Svidzinski TIF, Azeredo J, Oliveira R. Examination of potential virulence factors of Candida tropicalis clinical isolates from hospitalized patients. Mycopathologia 2010; 169: 175-182.
20. Tavanti A, Gow NA, Senesi S, Maiden MC, Odds FC. Optumization and validation of multilocus sequence typing for Candida albicans. J Clin Microbiol 2003; 41: 3765- 3776.
21. Gammelsrud KW, Lindstad BL, Gaustad P, Ingebretsen A, Hoiby EA, Sandven P, et al. Multilocus sequence typing of serial Candida albicans isolates from children with cancer, children with cystic fibrosis and healthy controls. Med Mycol 2012; 50: 619-626.
22. Feil EJ, Li BC, Aanensen DM, Hanage WP, Spratt BG. eBURST: inferring patterns of evolutionary descent among clusters of related bacterial genotypes from multilocus sequence typing data. J Bacteriol 2004; 186: 1518-1530.
23. Odds FC. Molecular phylogenetic and epidemiology of Candida albicans. Future Microbiol 2010; 5: 67-79.
24. Odds FC, Bougnoux ME, Shaw DJ, Bain JM, Davidson AD, Diogo D, et al. Molecular phylogenetics of Candida albicans. Eukaryot Cell 2007; 6: 1041-1052.
25. Heidrich D, Stopiglia CDO, Magagnin CM, Daboit TC, Vettorato G, Amaro TG, et al. Sixteen years of dermatomycosis caused by Candida spp. in the Metropolitan area of Porto Alegre, southern Brazil. Rev Inst Med Trop Sao Paulo 2016;58: 14.
26. Hamedifard M, Hashemi SJ, Daie Ghazvini R, Zareei M. Mycological study of superficial-cutaneous mycoses in Tehran, Iran. Infect Epidemiol Med 2017; 3: 60-65.
27. Afshar P, Khodavaisy S, Kalhori S, Ghasemi M, Razavyoon T, et al. Onychomycosis in north-east of Iran. Iran J Microbiol 2014; 6: 98-103.
28. Fallahi AA, Korbacheh P, Zaini F, Mirhendi H, Zeraati H, Noorbakhsh F, et al. Candida Species in cutaneous candidiasis patients in the Guilan province in Iran; identified by PCR-RFLP method. Acta Med Iran 2013; 51: 799-804.
29. Berenji F, Mahdavi Sivaki M, Sadabadi F, Andalib Aliabadi Z, Ganjbakhsh M, Salehi M. A retrospective study of cutaneous fungal infections in patients referred to Imam Reza Hospital of Mashhad, Iran during 2000-2011. Curr Med Mycol 2016; 2: 20-23.
30. Narain U, Bajaj AK. Candida onychomycosis: Indian scenario. Int J Adv Med 2016; 3:638-642.
31. Ghasemi Z, Hashemi SJ, Rezaei S, Kordbache P, Khosravi M, Mortazavi H, et al. Molecular analysis of Candida species with emphasis on predisposing factors in cutaneous candidiasis patients. Jundishapur J Microbiol 2016; 10 (2); e41030.
32. Feng X, Ling B, Yang G, Yu X, Ren D, Yao Z. Prevalence and distribution profiles of Candida parapsilosis, Candida orthopsilosis and Candida metapsilosis responsible for superficial candidiasis in a Chinese university hospital. Mycopathologia 2012; 173: 229-234.
33. Ge YP, Bockhout T, Zhan P, Lu GX, Shen YN, Li M. Characterization of the Candida parapsilosis complex in East china; species distribution differs among cities. Med Mycol 2012; 50: 56-66.
34. Whaley SG, Berkow EL, Rybak JM, Nishimoto A, Barker KS, Rogers PD. Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species. Front Microbiol 2016; 7:2173.
35. Mohamadi J, Motaghi M, Panahi J, Havasian MR, Delpisheh A, Azizian M. Antifungal resistance in Candida isolated from oral and diaper rash candidiasis in neonates. Bioinformation 2014; 10: 667-670.
36. Bruder- Nascimento A, Camargo CH, Mondelli AL, Bagagli E. Candida species biofilm and Candida albicans ALS3 polymorphisms in clinical isolates. Braz J Microbiol 2014;45: 1371-1377.
37. Costa CR, Passos XS, Souza LKH, Lucena PA, Fernandes OFL, Silva MRR. Differences in exoenzyme production and adherence ability of Candida spp. isolates from catheter, blood and oral cavity. Rev Inst Med Trop Sao Paulo 2010; 52: 139-143.
38. Junior AD, Silva AF, Rosa FC, Monteiro SG, Figueiredo PMS, Monteiro CA. In vitro differential activity of phospholipase and acid proteinases of clinical isolates of Candida. Rev Soc Bras Med Trop 2011; 44: 334-338.
39. Afsarian MH, Badali H, Boekhout T, Shokohi T, Katiraee F. Multilocus sequence typing of Candida albicans isolates from a burn intensive care unit in Iran. J Med Microbiol 2015; 64: 248-253.
40. Ge SH, Xie J, Xu J, Li J, Li DM, Zong LL, et al. Prevalence of specific and phylogenetically closely related genotypes in the population of Candida albicans associated with genital candidiasis in China. Fungal Genet Biol 2012; 49: 86-93.
2. Demiraslan H, Alabay S, Kilic AU, Borlu M, Doganay M. Cutaneous candidiasis caused by Candida glabrata in a HIV/AIDS patient. Int J STD AIDS 2013; 24:753-755.
3. Sadeghi G, Ebrahimi-Rad M, Mousavi SF, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M. Emergence of non-Candida albicans species: Epidemiology, phylogeny and fluconazole susceptibility profile. J Mycol Med 2018; 28: 51-58.
4. Amanloo S, Shams-Ghahfarokhi M, Ghahri M, Razzaghi-Abyaneh M. Genotyping of clinical isolates of Candida glabrata from Iran by multilocus sequence typing and determination of population structure and drug resistance profile. Med Mycol 2018; 56: 207-215.
5. Barchiesi F, Orsetti E, Gesuita R, Skrami E. Epidemiology, clinical characteristics, and outcome of candidemia in a tertiary referral center in Italy from 2010 to 2014. Infection 2016; 44: 205-213.
6. Fich F, Abarzúa-Araya A, Pérez M, Nauhm Y, León E. Candida parapsilosis and Candida guillermondii: Emerging pathogens in nail candidiasis. Indian J Dermatol 2014; 59: 24-29.
7. Pai V, Ganavalli A, Narayanshetty Kikkeri N. Antifungal resistance in dermatology. Indian J Dermatol 2018; 63: 361-368.
8. Dabiri M, Shams-Ghahfarokhia M, Razzaghi-Abyaneh M. Comparative analysis of proteinase, phospholipase, hydrophobicity and biofilm forming ability in Candida species isolated from clinical specimens. J Mycol Med 2018; 28: 437-442.
9. Odds FC, Jacobsen MD. Multilocus sequence typing of pathogenic Candida species. Eukaryot Cell 2008; 7: 1075-1084.
10. Su JZ, Yang YL, Rong R, Wu BQ. Genotype and homology analysis of pathogenic and colonization strains of Candida albicans from hospitalized neonates. Pediatr Neonatol 2018; 59: 488-493.
11. Bitar I, Khalaf RA, Harastani H, Tokajian S. Identification, typing, antifungal resistance profile, and biofilm formation of Candida albicans isolates from Lebanese hospital patients. Biomed Res Int 2014; 2014: 931372.
12. Tay ST, Tan HW, Na SL, Lim SL. Phenotypic and genotypic characterization of two closely related subgroups of Candida rugosa in clinical specimens. J Med Microbiol 2011; 60: 1591-1597.
13. Pfaller MA, Diekema DJ. Progress in antifungal susceptibility testing of Candida spp. by use of Clinical and Laboratory Standard Institute broth microdilution methods, 2010 to 2012. J Clin Microbiol 2012; 50: 2846-2856.
14. Clinical and Laboratory Standards Institute, Reference method for broth dilution antifungal susceptibility testing of yeasts; 4th informational supplement. CLSI document M27-S4. 2012; Wayne, PA, USA.
15. Razzaghi-Abyaneh M, Sadeghi G, Zeinali E, Alirezaee M, Shams-Ghahfarokhi M, Amani A. Species distribution and antifungal susceptibility of Candida spp. isolated from superficial candidiasis in outpatients in Iran. J Mycol Med 2014; 24(2):e43-50.
16. Zago CE, Silva S, Sanita PV, Borbugli PA, Improta Dias CM, Lordello VB. Dynamics of biofilm formation and the interaction between Candida albicans and methicillin- susceptible (MSSA) and –resistant Staphylococcus aureus (MRSA). PLoS One 2015; 10(4):e0123206.
17. Tsang CSP, Chu FCS, Leung WK, Jin LJ, Samaranayake LP, Siu SC. Phospholipase, proteinase and hemolytic activities of Candida albicans isolated from oral cavities of patients with type 2 diabetes mellitus. J Med Microbiol 2007; 56: 1393-1398.
18. Galan- Ladero MA, Blanco MT, Sacristan B, Fernandez- Calderon MC, Perez-Giraldo C, Gomez-Garcia AC. Enzymatic activities of Candida tropicalis isolated from hospitalized patients. Med Mycol 2010; 48: 207-210.
19. Negri M, Martins M, Henriques M, Svidzinski TIF, Azeredo J, Oliveira R. Examination of potential virulence factors of Candida tropicalis clinical isolates from hospitalized patients. Mycopathologia 2010; 169: 175-182.
20. Tavanti A, Gow NA, Senesi S, Maiden MC, Odds FC. Optumization and validation of multilocus sequence typing for Candida albicans. J Clin Microbiol 2003; 41: 3765- 3776.
21. Gammelsrud KW, Lindstad BL, Gaustad P, Ingebretsen A, Hoiby EA, Sandven P, et al. Multilocus sequence typing of serial Candida albicans isolates from children with cancer, children with cystic fibrosis and healthy controls. Med Mycol 2012; 50: 619-626.
22. Feil EJ, Li BC, Aanensen DM, Hanage WP, Spratt BG. eBURST: inferring patterns of evolutionary descent among clusters of related bacterial genotypes from multilocus sequence typing data. J Bacteriol 2004; 186: 1518-1530.
23. Odds FC. Molecular phylogenetic and epidemiology of Candida albicans. Future Microbiol 2010; 5: 67-79.
24. Odds FC, Bougnoux ME, Shaw DJ, Bain JM, Davidson AD, Diogo D, et al. Molecular phylogenetics of Candida albicans. Eukaryot Cell 2007; 6: 1041-1052.
25. Heidrich D, Stopiglia CDO, Magagnin CM, Daboit TC, Vettorato G, Amaro TG, et al. Sixteen years of dermatomycosis caused by Candida spp. in the Metropolitan area of Porto Alegre, southern Brazil. Rev Inst Med Trop Sao Paulo 2016;58: 14.
26. Hamedifard M, Hashemi SJ, Daie Ghazvini R, Zareei M. Mycological study of superficial-cutaneous mycoses in Tehran, Iran. Infect Epidemiol Med 2017; 3: 60-65.
27. Afshar P, Khodavaisy S, Kalhori S, Ghasemi M, Razavyoon T, et al. Onychomycosis in north-east of Iran. Iran J Microbiol 2014; 6: 98-103.
28. Fallahi AA, Korbacheh P, Zaini F, Mirhendi H, Zeraati H, Noorbakhsh F, et al. Candida Species in cutaneous candidiasis patients in the Guilan province in Iran; identified by PCR-RFLP method. Acta Med Iran 2013; 51: 799-804.
29. Berenji F, Mahdavi Sivaki M, Sadabadi F, Andalib Aliabadi Z, Ganjbakhsh M, Salehi M. A retrospective study of cutaneous fungal infections in patients referred to Imam Reza Hospital of Mashhad, Iran during 2000-2011. Curr Med Mycol 2016; 2: 20-23.
30. Narain U, Bajaj AK. Candida onychomycosis: Indian scenario. Int J Adv Med 2016; 3:638-642.
31. Ghasemi Z, Hashemi SJ, Rezaei S, Kordbache P, Khosravi M, Mortazavi H, et al. Molecular analysis of Candida species with emphasis on predisposing factors in cutaneous candidiasis patients. Jundishapur J Microbiol 2016; 10 (2); e41030.
32. Feng X, Ling B, Yang G, Yu X, Ren D, Yao Z. Prevalence and distribution profiles of Candida parapsilosis, Candida orthopsilosis and Candida metapsilosis responsible for superficial candidiasis in a Chinese university hospital. Mycopathologia 2012; 173: 229-234.
33. Ge YP, Bockhout T, Zhan P, Lu GX, Shen YN, Li M. Characterization of the Candida parapsilosis complex in East china; species distribution differs among cities. Med Mycol 2012; 50: 56-66.
34. Whaley SG, Berkow EL, Rybak JM, Nishimoto A, Barker KS, Rogers PD. Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species. Front Microbiol 2016; 7:2173.
35. Mohamadi J, Motaghi M, Panahi J, Havasian MR, Delpisheh A, Azizian M. Antifungal resistance in Candida isolated from oral and diaper rash candidiasis in neonates. Bioinformation 2014; 10: 667-670.
36. Bruder- Nascimento A, Camargo CH, Mondelli AL, Bagagli E. Candida species biofilm and Candida albicans ALS3 polymorphisms in clinical isolates. Braz J Microbiol 2014;45: 1371-1377.
37. Costa CR, Passos XS, Souza LKH, Lucena PA, Fernandes OFL, Silva MRR. Differences in exoenzyme production and adherence ability of Candida spp. isolates from catheter, blood and oral cavity. Rev Inst Med Trop Sao Paulo 2010; 52: 139-143.
38. Junior AD, Silva AF, Rosa FC, Monteiro SG, Figueiredo PMS, Monteiro CA. In vitro differential activity of phospholipase and acid proteinases of clinical isolates of Candida. Rev Soc Bras Med Trop 2011; 44: 334-338.
39. Afsarian MH, Badali H, Boekhout T, Shokohi T, Katiraee F. Multilocus sequence typing of Candida albicans isolates from a burn intensive care unit in Iran. J Med Microbiol 2015; 64: 248-253.
40. Ge SH, Xie J, Xu J, Li J, Li DM, Zong LL, et al. Prevalence of specific and phylogenetically closely related genotypes in the population of Candida albicans associated with genital candidiasis in China. Fungal Genet Biol 2012; 49: 86-93.
| Files | ||
| Issue | Vol 11 No 4 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v11i4.1463 | |
| Keywords | ||
| Candida species Candidiasis Molecular epidemiology Virulence factors Antifungal susceptibility Multilocus sequence typing | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Sadeghi G, Ebrahimi-Rad M, Shams-Ghahfarokhi M, Jahanshiri Z, Mirabzadeh Ardakani E, Eslamifar A, Mousavi SF, Razzaghi-Abyaneh M. Cutaneous candidiasis in Tehran-Iran: from epidemiology to multilocus sequence types, virulence factors and antifungal susceptibility of etiologic Candida species. Iran J Microbiol. 2019;11(4):267-279.
