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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]

Candida albicans can cause infections ranging from superficial skin infections to life-threateningsystemic infections in immunocompromised hosts. Although several C. albicans virulence factorsare widely discussed in great detail, intrinsic host determinants that are critical for C. albicanspathogenesis remain less interested and poorly understood. In view of this, a model of Caenorhabditiselegans was used to study host longevity and immunity in response to C. albicans pathogenesis.The influence of C. albicans in pathological and survival aspects was evaluated using C. elegans.C. albicans hyphal formation in different C. elegans genetic backgrounds was evaluated. Moreover,several C. elegans fluorescent proteins as gene expression markers upon C. albicans infectionswere evaluated. C. albicans is pathogenic to C. elegans and reduces the lifespan of C. elegans inassociation with repression of the insulin/IGF-1-like signaling (IIS) pathway. Moreover, repressionof DAF-16/forkhead transcription factor increases aggressiveness of C. albicans by enhancing hyphalformation. In addition, infection of C. albicans increases lipofuscin accumulation, promotes DAF-16nuclear translocation, increases superoxide dismutase (SOD-3) expression, which coordinately linksbetween aging and innate immunity. Thus, we demonstrate here the strategy to utilize C. elegans asa model host to elucidate host genetic determinants that provide insights into the pathogenesis ofC. albicans infections.

Soil fungal communities play an important role in regulating biogeochemical transformations, yet soil-related fungal pathogens are emerging threats to humans. Our previous studies have revealed the pathogenic Scedosporium species in soils samples from public parks with high human activities in Thailand. However, measurement and survey of soil fungal communities in other areas with high human/animal activities, such as the pigsty, are poorly determined. In this study, soil fungal pathogens from a pigsty were isolated and identified. Soil samples were collected from the surrounding drainage areas. Fungal species were identified using morphological and molecular analyses. Isolation of soil samples from the pigsty revealed at least 11 species that have been identified. The most abundant fungal species belonged to genera Aspergillus and Penicillium. Moreover, Scedo-Select III culturing and phylogenetic analysis with β-tubulin gene sequencing revealed the three environmental isolates of Scedosporium species, which were consistent with the S.apiospermum. These three Scedosporium isolates were susceptible to voriconazole and caused pathological characteristics of scedosporiosis similar to S. apiospermum in vivo. In conclusion, our findings contribute towards a better understanding of soil-borne pathogenic fungi in the pigsty. The isolation of Scedosporium species with pathogenic potentials in the present study can be beneficial for the management of public health surveillance, epidemiologists, as well as physicians to reduce the risk of soil fungal contamination among pigsty workers.

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.

This study examines the ability of the quorum-sensing molecules (QSMs) farnesol and tryptophol to induce programmed cell death of the pathogenic fungus Candida albicans, to alter the expression of apoptosis-related genes, and to reduce the pathogenicity and virulence of C. albicans in Galleria mellonella. Our results showed that both farnesol and tryptophol inhibited C. albicans germ tube formation. In the QSM-treated group, the expression levels of the apoptosis genes increased, whereas the expression level of the anti-apoptosis gene decreased. Further, pretreatment of C. albicans with tryptophol or farnesol prior to G. mellonella larval infection significantly enhanced host survival compared with larvae infected with untreated C. albicans. Thus, farnesol and tryptophol may trigger apoptosis of C. albicans in vitro and reduce the virulence of C. albicans in vivo. Although further study is needed to identify the precise mechanisms underlying the antifungal properties of farnesol and tryptophol, these results suggest that QSMs may be effective agents for controlling fungal infection.

C. albicans is one of the most important species of fungi known to produce biofilms on installed medical devices. The environment surrounding the fungi influences the development of the biofilm. Temperature is known to affect the yeast-to-hypha transition of C. albicans, but the impact of this factor on biofilm formation is still not understood. This study aimed to investigate the effects of temperature (42°C versus 37°C) on the formation of C. albicans biofilms. Three reference C. albicans strains were used: SC 5314, ATCC 90028, and ATCC 96901. Biofilm development was monitored in a series of time intervals, 2, 4, 6, 8, 24, and 48 h, at both 37°C and 42°C. Biofilm formation under each condition was evaluated by scanning electron microscopy, crystal violet staining, and 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-(phenylamino)-carbonyl-2H-tetrazoliumhydroxide reduction assay. Our results demonstrated that at 42°C, tested strains of C. albicans could produce a biofilm, but the mass, thickness, and metabolic activity were lower than those of the biofilm formed at 37°C.

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.