Abstract

Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency disorder characterised by susceptibility to chronic Candida and fungal dermatophyte infections of the skin, nails and mucous membranes. Molecular epidemiology studies of CMC infection are limited in number and scope and it is not clear whether single or multiple strains inducing CMC persist stably or are exchanged and replaced. We subjected 42 C. albicans individual single colony isolates from 6 unrelated CMC patients to multilocus sequence typing (MLST). Multiple colonies were typed from swabs taken from multiple body sites across multiple time points over a 17-month period. Among isolates from each individual patient, our data show clonal and persistent diploid sequence types (DSTs) that were stable over time, identical between multiple infection sites and exhibit azole resistant phenotypes. No shared origin or common source of infection was identified among isolates from these patients. Additionally, we performed C. albicans MLST SNP genotype frequency analysis to identify signatures of past loss of heterozygosity (LOH) events among persistent and azole resistant isolates retrieved from patients with autoimmune disorders including CMC.

Highlights

  • Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency disorder characterised by susceptibility to Candida spp. infection of the skin, nails and mucous membranes

  • Presenting as chronic localised lesions, CMC persists due to isolated primary immune defects or secondary to predisposing immune compromising conditions such as HIV. It can present as a heterogeneous disorder such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), as a multisystem syndrome with hyper immunoglobin E syndrome (HEIS) or hypothyroidism, and can be complicated by additional autoimmune conditions such as inflammatory bowel disease (IBD) [1,2,3]

  • multilocus sequence typing (MLST) analysis was performed on 42 C. albicans isolates from 6 CMC patients collected over a period of 17 months

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Summary

Introduction

Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency disorder characterised by susceptibility to Candida spp. infection of the skin, nails and mucous membranes. It manifests separately to vulvovaginal candidiasis and rarely as invasive candidiasis. Presenting as chronic localised lesions, CMC persists due to isolated primary immune defects or secondary to predisposing immune compromising conditions such as HIV. It can present as a heterogeneous disorder such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), as a multisystem syndrome with hyper immunoglobin E syndrome (HEIS) or hypothyroidism, and can be complicated by additional autoimmune conditions such as inflammatory bowel disease (IBD) [1,2,3]. Immunological surveillance of potential invasive microorganisms involves immune recognition of the pathogen and activation of innate and adaptive immune.

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