Abstract
Candida albicans is a commensal fungal pathogen that is often found as part of the human microbial flora. The aim of the present study was to establish a relationship between diverse genotypes and phenotypes of clinical isolates of C. albicans. Totally 231 clinical isolates were collected and used for genotyping and phenotypic switching analysis. Based on the microsatellite locus (CAI) genotyping assay, 65 different genotypes were identified, and some dominant types were found in certain human niches. For example, the genotypes of 30–44 and 30–45 were enriched in vaginal infection samples. C. albicans has a number of morphological forms including the single-celled yeasts, multicellular filaments, white, and opaque cell types. The relationship between the CAI genotype and the ability to undergo phenotypic switching was examined in the clinical isolates. We found that the strains with longer CAA/G repeats in both alleles of the CAI locus were more opaque competent. We also discovered that some MTL heterozygous (a/alpha) isolates could undergo white–opaque switching when grown on regular culture medium (containing glucose as the sole carbon source). Our study establishes a link between phenotypic switching and genotypes of the CAI microsatellite locus in clinical isolates of C. albicans.
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References
Berman J (2012) Candida albicans. Curr Biol 22:R620–R622. doi:10.1016/j.cub.2012.05.043
Biswas S, Van Dijck P, Datta A (2007) Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans. Microbiol Mol Biol Rev 71:348–376. doi:10.1128/MMBR.00009-06
Bougnoux ME, Tavanti A, Bouchier C, Gow NA, Magnier A, Davidson AD, Maiden MC, D’Enfert C, Odds FC (2003) Collaborative consensus for optimized multilocus sequence typing of Candida albicans. J Clin Microbiol 41:5265–5266
Du H, Huang G (2015) Environmental pH adaption and morphological transitions in Candida albicans. Curr Genet. doi:10.1007/s00294-015-0540-8
Fan SR, Bai FY, Liao QP, Liu ZH, Li J, Liu XP (2008) Genotype distribution of Candida albicans strains associated with different conditions of vulvovaginal candidiasis, as revealed by microsatellite typing. Sex Transm Infect 84:103–106. doi:10.1136/sti.2007.025700
Ge SH, Wan Z, Li J, Xu J, Li RY, Bai FY (2010) Correlation between azole susceptibilities, genotypes, and ERG11 mutations in Candida albicans isolates associated with vulvovaginal candidiasis in China. Antimicrob Agents Chemother 54:3126–3131. doi:10.1128/AAC.00118-10
Ge SH, Xie J, Xu J, Li J, Li DM, Zong LL, Zheng YC, Bai FY (2012) Prevalence of specific and phylogenetically closely related genotypes in the population of Candida albicans associated with genital candidiasis in China. Fungal Genet Biol FG B 49:86–93. doi:10.1016/j.fgb.2011.10.006
Huang G (2012) Regulation of phenotypic transitions in the fungal pathogen Candida albicans. Virulence 3(3):251–261. doi:10.4161/viru.20010
Huang G, Srikantha T, Sahni N, Yi S, Soll DR (2009) CO(2) regulates white-to-opaque switching in Candida albicans. Curr Biol 19:330–334. doi:10.1016/j.cub.2009.01.018
Huang G, Yi S, Sahni N, Daniels KJ, Srikantha T, Soll DR (2010) N-acetylglucosamine induces white to opaque switching, a mating prerequisite in Candida albicans. PLoS Pathog 6:e1000806. doi:10.1371/journal.ppat.1000806
Li J, Fan SR, Liu XP, Li DM, Nie ZH, Li F, Lin H, Huang WM, Zong LL, Jin JG, Lei H, Bai FY (2008) Biased genotype distributions of Candida albicans strains associated with vulvovaginal candidosis and candidal balanoposthitis in China. Clin Infect Dis Off Publ Infect Dis Soc Am 47:1119–1125. doi:10.1086/592249
Liu H, Kohler J, Fink GR (1994) Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science 266:1723–1726
Lockhart SR, Pujol C, Daniels KJ, Miller MG, Johnson AD, Pfaller MA, Soll DR (2002) In Candida albicans, white–opaque switchers are homozygous for mating type. Genetics 162:737–745
Lyon JP, Moraes KC, Moreira LM, Aimbire F, de Resende MA (2010) Candida albicans: genotyping methods and clade related phenotypic characteristics. Braz J Microbiol [Publ Braz Soc Microbiol] 41:841–849. doi:10.1590/S1517-83822010000400003
Magee BB, Magee PT (2000) Induction of mating in Candida albicans by construction of MTLa and MTLalpha strains. Science 289:310–313 (8662 [pii])
Mathe L, Van Dijck P (2013) Recent insights into Candida albicans biofilm resistance mechanisms. Curr Genet 59:251–264. doi:10.1007/s00294-013-0400-3
Miller MG, Johnson AD (2002) White–opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Cell 110:293–302 (S0092867402008371 [pii])
Odds FC, Hanson MF, Davidson AD, Jacobsen MD, Wright P, Whyte JA, Gow NA, Jones BL (2007) One year prospective survey of Candida bloodstream infections in Scotland. J Med Microbiol 56:1066–1075. doi:10.1099/jmm.0.47239-0
Pfaller MA, Diekema DJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20:133–163. doi:10.1128/CMR.00029-06
Sampaio P, Gusmao L, Alves C, Pina-Vaz C, Amorim A, Pais C (2003) Highly polymorphic microsatellite for identification of Candida albicans strains. J Clin Microbiol 41:552–557
Sampaio P, Gusmao L, Correia A, Alves C, Rodrigues AG, Pina-Vaz C, Amorim A, Pais C (2005) New microsatellite multiplex PCR for Candida albicans strain typing reveals microevolutionary changes. J Clin Microbiol 43:3869–3876. doi:10.1128/JCM.43.8.3869-3876.2005
Shimizu K, Hattori H, Adachi H, Oshima R, Horii T, Tanaka R, Yaguchi T, Tomita Y, Akiyama M, Kawamoto F, Kanbe T (2011) Microsatellite-based genotyping of Candida albicans isolated from patients with superficial candidiasis. Med Mycol J 52:129–138. doi:10.3314/jjmm.52.129
Slutsky B, Staebell M, Anderson J, Risen L, Pfaller M, Soll DR (1987) “White–opaque transition”: a second high-frequency switching system in Candida albicans. J Bacteriol 169:189–197
Sudbery P, Gow N, Berman J (2004) The distinct morphogenic states of Candida albicans. Trends Microbiol 12:317–324. doi:10.1016/j.tim.2004.05.008
Tao L, Du H, Guan G, Dai Y, Nobile CJ, Liang W, Cao C, Zhang Q, Zhong J, Huang G (2014) Discovery of a “white-gray-opaque” tristable phenotypic switching system in candida albicans: roles of non-genetic diversity in host adaptation. PLoS Biol 12:e1001830. doi:10.1371/journal.pbio.1001830
Whiteway M, Bachewich C (2007) Morphogenesis in Candida albicans. Annu Rev Microbiol 61:529–553. doi:10.1146/annurev.micro.61.080706.093341
Xie J, Tao L, Nobile CJ, Tong Y, Guan G, Sun Y, Cao C, Hernday AD, Johnson AD, Zhang L, Bai FY, Huang G (2013) White–opaque switching in natural MTLa/alpha isolates of Candida albicans: evolutionary implications for roles in host adaptation, pathogenesis, and sex. PLoS Biol 11:e1001525. doi:10.1371/journal.pbio.1001525
Acknowledgments
This work was supported by Grants from the Chinese National Natural Science Foundation (31370175, 31170086 and 81322026 to G. H.; 31200115 to L. T.; 81201267 to H. L.) and the “100 Talent Program’’ Grant from the Chinese Academy of Sciences (to G. H.).
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Communicated by M. Kupiec.
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Hu, J., Guan, G., Dai, Y. et al. Phenotypic diversity and correlation between white–opaque switching and the CAI microsatellite locus in Candida albicans . Curr Genet 62, 585–593 (2016). https://doi.org/10.1007/s00294-016-0564-8
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DOI: https://doi.org/10.1007/s00294-016-0564-8