Host genetic signatures of susceptibility to fungal disease

Our relative inability to predict the development of fungal disease and its clinical outcome raises fundamental questions about its actual pathogenesis. Several clinical risk factors are described to predispose to fungal disease, particularly in immunocompromised and severely ill patients. However, these alone do not entirely explain why, under comparable clinical conditions, only some patients develop infection. Recent clinical and epidemiological studies have reported an expanding number of monogenic defects and common polymorphisms associated with fungal disease. By directly implicating genetic variation in the functional regulation of immune mediators and interacting pathways, these studies have provided critical insights into the human immunobiology of fungal disease. Most of the common genetic defects reported were described or suggested to impair fungal recognition by the innate immune system. Here, we review common genetic variation in pattern recognition receptors and its impact on the immune response against the two major fungal pathogens Candida albicans and Aspergillus fumigatus. In addition, we discuss potential strategies and opportunities for the clinical translation of genetic information in the field of medical mycology. These approaches are expected to transfigure current clinical practice by unleashing an unprecedented ability to personalize prophylaxis, therapy and monitoring for fungal disease.This work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014 to AC, and SFRH/BPD/96176/2013 to CC), the Institut Mérieux (Mérieux Research Grant 2017 to CC), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Research Grant 2017 to AC)

Mannose-binding lectin gene polymorphism, vulvovaginal candidiasis, and bacterial vaginosis

OBJECTIVE: To evaluate associations between polymorphisms in the gene coding for mannose-binding lectin (MBL) and the diagnosis of acute or recurrent vulvovaginal candidiasis and bacterial vaginosis METHODS: Women at two outpatient clinics in Brazil filled out a questionnaire and were examined for the presence of vulvovaginal candidiasis or bacterial vaginosis. A buccal swab was blindly tested for codons 54 and 57 MBL2 gene polymorphisms by polymerase chain reaction and endonuclease digestion. RESULTS: A total of 177 women were enrolled. Vulvovaginal candidiasis was identified in 78 (44.1%) women, 33 (18.6%) had bacterial vaginosis, and 66 (37.3%) were normal controls. Recurrent vulvovaginal candidiasis was present in 50 (64.1%) of the women with vulvovaginal candidiasis; 20 (60.6%) of the bacterial vaginosis patients had recurrent disease. Vulvovaginal candidiasis was associated with white race (P=.007), bacterial vaginosis was associated with nonwhite race (P=.05), and both were associated with a history of allergy (P <=.02) and having sexual intercourse at least three times a week (P<.001). Carriage of the variant MBL2 codon 54 allele B was more frequent in women with recurrent vulvovaginal candidiasis (25.0%) than in the women with acute vulvovaginal candidiasis (17.9%) or controls (10.6%) (P=.004). Allele B was also more prevalent in women with recurrent bacterial vaginosis (22.5%) than in those with acute bacterial vaginosis (0%) (P=.009). The MBL2 codon 57 polymorphism was infrequent and not associated with vulvovaginal candidiasis or bacterial vaginosis. CONCLUSION: The incidence of vulvovaginal candidiasis and bacterial vaginosis differs by ethnicity in Brazilian women. The MBL2 codon 54 gene polymorphism is associated with both recurrent vulvovaginal candidiasis and recurrent bacterial vaginosis.10951123112