Biological and genomic analyses of a clinical isolate of Yarrowia galli from China.

Infections caused by emerging fungal pathogens represent a new threat to human health. The yeast Yarrowia (Candida) galli was first described from chicken breast and liver in 2004 and has occasionally been isolated in clinical settings. In this study, we present the first report of a Y. galli isolate from a face granuloma of a woman. Y. galli is unable to grow at human physiological temperature (37 °C). Phenotypic analysis demonstrates that Y. galli can exist as several morphological types, namely fluffy, sticky, tight, and yeast forms, based on their cellular and colony appearances. Interestingly, Y. galli is able to undergo switching among different morphologies. These morphological changes are similar to the switching systems in pathogenic Candida species such as Candida albicans and Candida tropicalis. We further sequenced the genome of the Y. galli isolate. A comparative analysis with pathogenic yeast species indicated that a set of lipid metabolism genes were enriched in Y. galli. Domain enrichment analysis demonstrated that, similar to Candida clade species, the genome of Y. galli maintained several gene families required for virulence. Our biological and genomic analyses provide new insights into the understanding of the biology of Y. galli as either an environmental isolate or a potential human pathogen.

The effects of clioquinol in morphogenesis, cell membrane and ion homeostasis in Candida albicans.

BACKGROUND: Candida albicans is the most prevalent opportunistic fungal pathogen. Development of antifungals with novel targets is necessary for limitations of current antifungal agents and the emergence of drug resistance. The antifungal activity of clioquinol was widely accepted while the precise mechanism was poorly understood. Hence, we aimed to seek for the possible mechanism of clioquinol against Candida albicans in the present study. RESULTS: Clioquinol could inhibit hyphae formation in a concentration-dependent manner in multiple liquid and solid media. The concentration and time-dependent anti-biofilm activities were observed in different incubation periods quantitatively and qualitatively. Further investigation found that clioquinol disrupted cell membrane directly in high concentration and induced depolarization of the membrane in low concentration. As for the influence on ion homeostasis, the antifungal effects of clioquinol could be reversed by exogenous addition of metal ions. Meanwhile, the minimum inhibitory concentration of clioquinol was increased in media supplemented with exogenous metal ions and decreased in media supplemented with exogenous metal chelators. We also found that the cellular labile ferrous iron level decreased when fungal cells were treated with clioquinol. CONCLUSION: These results indicated that clioquinol could inhibit yeast-hyphae transition and biofilm formation in Candida albicans. The effect on the cell membrane was different depending on different concentrations of clioquinol. Meanwhile, clioquinol could interfere with ion homeostasis as metal chelators for zinc, copper and iron, which was quite different with current common antifungal agents. All in all, clioquinol can be a new promising antifungal agent with novel target though more studies are needed to better understand the precise antifungal mechanism.

Chromoblastomycosis Caused by Fonsecaea nubica: First Report in Northern China and Literature Review.

Chromoblastomycosis is found worldwide with higher incidence in tropical and subtropical regions. Fonsecaea spp. is one of the major causative agents of this disease. First case of chromoblastomycosis due to Fonsecaea nubica in Northern China is reported in a 75-year-old Chinese male. We firstly summarized molecular identification methods of Fonsecaea spp. and all the strains of F. nubica reported in the literature. Sequencing of internal transcribed spacer alone and/or combined with actin (ACT1), partial cell division cycle (CDC42) and partial beta-tubulin (BT2) were most commonly used to identify species, while lactase (Lac), homogentisate (HmgA) and polyketide synthase (PKS1) were also used in some cases. Most strains were isolated from South America and Eastern China. Five clinical cases of chromoblastomycosis due to F. nubica from Asia and Europe were also reviewed. All the five patients were male, over 30 years old, and their lesions occurred after trauma.

Clioquinol influences cell membrane, attenuates virulence factors, induces apoptosis to inhibit Candida albicans growth.

Aim: To investigate the antifungal mechanism of clioquinol and indicate that clioquinol has potential as a novel therapeutic antifungal agent.Materials & methods: Analyze differentially expressed genes of Candida albicans treated with clioquinol using RNA-sequencing. The effects on cell wall and membrane features, virulence factors, apoptosis-induced cell death were also investigated.Results: The differentially expressed genes of C. albicans after treated with clioquinol focused on cell wall and membrane synthesis, antioxidant system and energy metabolism. Clioquinol did not change cell wall components levels while it decreased squalene epoxidase activity to influence the ergosterol biosynthesis in cell membrane. It also decreased cellular surface hydrophobicity and induced ß-glucan unmasking to attenuate virulence factors. Meanwhile, clioquinol influenced enzyme activities involved in antioxidant system, citrate cycle, oxidative phosphorylation and decreased the ATP levels. Clioquinol induced apoptosis in C. albicans to exert its fungicidal activity. It induced reactive oxygen species and calcium ion elevation, leading to loss of mitochondrial membrane potential, cytochrome C release, metacaspase activation, thereby triggering apoptosis.Conclusion: Clioquinol exerted anti-C. albicans activity through influencing cell membrane, attenuating virulence factors and inducing apoptosis.

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Clinical parameters associated with severity of nail psoriasis and therapeutic efficacy.

BACKGROUND: Nail involvement is common in psoriasis patients, however, there are few detailed studies of clinical parameters related to disease severity and therapeutic efficacy. OBJECTIVES: Our retrospective study aimed to describe the prevalence and clinical characteristics in nail psoriasis patients and determine possible associations between multiple clinical parameters and disease severity or therapeutic efficacy. MATERIALS AND METHODS: A total of 89 nail psoriasis patients were included and investigated using dermoscopy. The Nail Psoriasis Severity Index (NAPSI) and the Nijmegen-Nail Psoriasis Activity Index tool (N-NAIL) were used to measure the severity and improvement of nail psoriasis. Severity and efficacy-related parameters were also analysed. RESULTS: Subungual hyperkeratosis (94.4%) was the most commonly observed nail feature. Coexistence of pitting and leukonychia, transverse grooves and thickening were more commonly observed in juveniles than adults. Patients with more severe nail psoriasis were more likely to have more nails affected and develop discolouration. The efficacy of treatment after fixed intervals of treatment was analysed. Most clinical parameters were not related to therapeutic efficacy, including disease duration, age at onset and number of nail signs. However, after six months of treatment, the presence of transverse grooves was shown to be associated with better efficacy. Based on comparison of NAPSI and N-NAIL scores relative to the first visit, the presence of transverse grooves, longitudinal ridges or discolouration were associated with better efficacy. CONCLUSION: Clinicians should be aware of the clinical parameters related to severity and the use of therapeutic efficacy in choosing individualized treatment and predicting prognosis.