Microbiological Screening of Irish Patients with Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Reveals Persistence of Candida albicans Strains, Gradual Reduction in Susceptibility to Azoles, and Incidences of Clinical Signs of Oral Candidiasis without Culture Evidence

Abstract

Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) are prone to chronic mucocutaneous candidiasis, which is often treated with azoles. The purpose of this study was to characterize the oral Candida populations from 16 Irish APECED patients, who comprise approximately half the total number identified in Ireland, and to examine the effect of intermittent antifungal therapy on the azole susceptibility patterns of Candida isolates. Patients attended between one and four clinical evaluations over a 5-year period, providing oral rinses and/or oral swab samples each time. Candida was recovered from 14/16 patients, and Candida albicans was the only Candida species identified. Interestingly, clinical diagnosis of candidiasis did not correlate with microbiological evidence of Candida infection at 7/22 (32%) clinical assessments. Multilocus sequence typing analysis of C. albicans isolates recovered from the same patients on separate occasions identified the same sequence type each time. Fluconazole resistance was detected in isolates from one patient, and isolates exhibiting a progressive reduction in itraconazole and/or fluconazole susceptibility were identified in a further 3/16 patients, in each case correlating with the upregulation of CDR-and MDR-encoded efflux pumps. Mutations were also identified in the ERG11 and the TAC1 genes of isolates from these four patients; some of these mutations have previously been associated with azole resistance. The findings suggest that alternative Candida treatment options, other than azoles such as chlorhexidine, should be considered in APECED patients and that clinical diagnosis of oral candidiasis should be confirmed by culture prior to the commencement of anti-Candida therapy.

Genotyping Candida albicans from Candida Leukoplakia and Non-Candida Leukoplakia Shows No Enrichment of Multilocus Sequence Typing Clades but Enrichment of ABC Genotype C in Candida Leukoplakia

“…No ABC genotype C isolates were identified in the periodontal study. In a separate study on 14 oral C. albicans -positive patients with Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome, a rare genetic disease characterised by autoimmunity to endocrine organs, ectodermal disorders and chronic mucocutaneous candidiasis, 9/14 patients yielded genotype A isolates, six of which belonged to MLST clade 1 [30]. One patient yielded genotype B isolates (MLST clade 8) and four patients yielded genotype C isolates, two of which belonged to MLST clade 4, one to clade 15, whereas the remaining isolate was a singleton.…”

Enrichment of Multilocus Sequence Typing Clade 1 with Oral Candida albicans Isolates in Patients with Untreated Periodontitis

“…The extraction of DNA from Candida isolates for PCRs was performed as described previously by McManus et al (17).…”

Investigating Clinical Issues by Genotyping of Medically Important Fungi: Why and How?

“…The persistence of the same strain type at different site locations or over long periods of time seems to be the most common scenario (131). However, if an adaptive response to a particular environment is needed, the strain may undergo microevolution (132,141,(150)(151)(152)(153). These genetic variations have been widely observed among closely related strains and are mainly associated with loss of heterozygosity (120,124,125,144).…”