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Candida albicans is an opportunistic fungal infectious agent that can cause cutaneous candidiasis in humans. Biofilms formation of C. albicans is thought to be the major cause of antifungal drug resistance. Despite numerous studies conducted on C. albicans biofilms, a comprehensive understanding of how C. albicans biofilms induced cutaneous candidiasis in humans and the development of a more effective targeted therapy remain poorly investigated. Available animal models of cutaneous candidiasis and in vitro human skin cell cultures do not fully reflect the actual human skin microenvironment or the disease pathogenesis. We investigated the molecular pathology of C. albicans infection using an in vitro biofabricated 3D skin. This in vitro biofabricated 3D skin comprises a fully humanized three-dimensional (3D) skin equivalent, consisting of a stratified terminally differentiated epidermis and an underlying dermal compartment. Antifungal drug susceptibility testing, histological and electron microscopy study, biofilms study, and pro-inflammatory cytokines analysis were conducted in C. albicans infected skin. Histological results revealed that C. albicans covered and produced biofilm on the in vitro biofabricated 3D skin, invading the skin compartments including epidermis and dermis. Elevation of proinflammatory cytokines including MMP-9, IL-1β, TNF-α, and IL-5 were examined in the C. albicans infected skin. However, treatment with itraconazole reduced the pathology of C. albicans infection. This study provides an alternative pathological model of cutaneous candidiasis, which can physiologically represent a close-up event during C. albicans. Moreover, it is rapid, cost-effective, and reproducible of the in vitro biofabricated 3D skin model, and may further highlight the importance of utilizing in vivo-like conditions to improve high-throughput screening for drug discovery against several antifungal drug resistant pathogens.

Dermatophytes comprising the genera Trichophyton, Microsporum, and Epidermophyton are important causes of superficial mycoses. The number of infected patients and the distribution of species of these organisms in our hospital were unknown. We therefore aimed to investigate the clinical pattern of dermatophyte infections and to identify the species of these dermatophytes at the Dermatological Clinic of the Hospital for Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok in a 1-year period. Twenty-six patients who had typical dermatophytosis lesions were recruited (27 specimens); 17 were female (65.38%) and 9 (34.62%) were male. The age range of the patients was 16-92 years. In total, nine dermatophyte isolates were identified by macroscopic and microscopic morphological characteristics. We found Microsporum canis (four isolates), Trichophyton mentagrophytes complex (one), Trichophyton rubrum (two), Trichophyton verrucosum (one), and Trichophyton tonsurans (one). The in vitro susceptibility profiles of seven antifungal agents against the nine dermatophytes were as follows (minimum inhibitory concentration ranges in μg/ml): The results were as follows (MIC ranges in μg/ml): ciclopirox, ≤0.06-0.5, griseofulvin ≤0.06-0.5, itraconazole ≤0.002-0.06, posaconazole ≤0.015-0.03, voriconazole ≤0.02-≥1, fluconazole ≤0.08-8, and terbinafine ≤0.01-0.125. This study represents the current state of dermatophyte infections in a metropolitan area of Bangkok, Thailand.

Scedosporium boydii and Lomentospora prolificans are filamentous fungi reported to cause infection in immunocompromized individuals. We studied the effect of farnesol to inhibit growth of S. boydii and L. prolificans by measuring colony diameter and determining minimal effective concentration (MEC). S. boydii and L. prolificans were grown on Sabouraud dextrose agar (SDA) at 37oC for 5 days. Conidia were collected and adjusted to a concentration of 104 conidia/ ml. Twenty microliters of conidia suspension was placed in each well of a sixwell plate containing serial dilutions of farnesol (10 μM, 100 μM, 1,000 μM, and 10,000 μM) in SDA. Colony morphology and diameter were observed on days 1, 2, 3, and 4. Farnesol at concentrations of 1,000 μM or higher caused the colony diameter of both S. boydii and L. prolificans to be smaller than untreated controls in a dose-dependent manner. The MEC of farnesol to inhibit growth of both S. boydii and L. prolificans was 3.2 mM. This study reveals the antifungal property of farnesol against S. boydii and L. prolificans, which can be used for further study as an alternative antifungal agent against these fungal infections.

Background and purpose: Subcutaneous infections caused by Scedosporium apiospermum present as chronic eumycetomatous manifestations in both immunocompromised and immunocompetent individuals. Serious adverse effects/toxicities from the long-term use of antifungal drugs and antifungal resistance have been reported in patients with S. apiospermum infections. The present study aimed to determine the anti-S. apiospermum activities of fungal quorum sensing molecule known as tryptophol (TOH) and to develop a TOH-containing emulgel for treating S. apiospermum eumycetoma. Experimental approach: Anti-S. apiospermum activities of TOH were determined and compared with voriconazole. Effects of TOH on S. apiospermum biofilm formation and human foreskin fibroblast (HFF)-1 cell cytotoxicity were determined. Moreover, TOH-containing emulgel was developed and physical properties, in vitro, and in vivo antifungal activities against S. apiospermum eumycetoma were evaluated. Findings/Results: The minimal concentration of TOH at 100 µM exhibited anti-S. apiospermum activities by reducing growth rate, germination rate, and biofilm formation with less cytotoxicity to HFF-1 cells than voriconazole. Further study on the development of an emulgel revealed that TOH-containing emulgel exhibited excellent physical properties including homogeneity, consistency, and stability. Treatment by TOH-containing emulgel significantly reduced subcutaneous mass in a mouse model of S. apiospermum eumycetoma. The histopathological assessment showed marked improvement after 14 days of TOH-containing emulgel treatment. Conclusion and implications: TOH could be used as an anti-fungal agent against S. apiospermum infections. A novel and stable TOH-containing emulgel was developed with excellent anti-S. apiospermum activities suggesting the utilization of TOH-containing emulgel as an innovative therapeutic approach in the treatment of S. apiospermum eumycetoma. [ABSTRACT FROM AUTHOR]