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Tryptophol (TOH), a fungal quorum-sensing molecule, that possesses anti-fungal activities for controlling the growth of human pathogenic fungi. In the present study, we developed TOH-containing emulgel formulations and examined the antifungal activities and potential use as topical treatments on the skin. The results showed that TOH-containing emulgel at 1000 μM has excellent physical characteristics as homogenous, stability, and inhibits the growth of 30 species of human pathogenic fungi in vitro. TOH-containing emulgel did not cause skin irritation in mouse model of irritation and in healthy human volunteers. Moreover, an increase in skin hydration and a decrease in trans-epidermal water loss (TEWL) were observed after TOH-containing emulgel treatment on human skin. Our findings indicated that TOH-containing emulgel can be utilize as an antifungal agent for topical treatment against fungal infections on the skin. [ABSTRACT FROM AUTHOR]

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]

Background: Cryptococcosis is a life-threatening infection is primarily caused by two sibling species Cryptococcus neoformans and Cryptococcus gattii. Several virulence-related factors of these cryptococci have been widely investigated in Caenorhabditis elegans, representing a facile in vivo model of host–pathogen interaction. While recent studies elucidated cryptococcal virulence factors, intrinsic host factors that affect susceptibility to infections by cryptococci remain unclear and poorly investigated. Results: Here, we showed that defects in C. elegans insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS) pathway influenced animal lifespan and mechanisms of host resistance in cryptococcal infections, which required the activation of aging regulator DAF-16/Forkhead box O transcription factor. Moreover, accumulation of lipofuscin, DAF-16 nuclear localization, and expression of superoxide dismutase (SOD-3) were elevated in C. elegans due to host defenses during cryptococcal infections. Conclusion: The present study demonstrated the relationship between longevity and immunity, which may provide a possibility for novel therapeutic intervention to improve host resistance against cryptococcal infections. [ABSTRACT FROM AUTHOR]

Scedosporium is a genus comprising at least 10 species of airborne fungi (saprobes) that survive and grow on decaying organic matter. These fungi are found in high density in human-affected areas such as sewage-contaminated water, and five species, namely Scedosporium apiospermum, S. boydii, S. aurantiacum, S. dehoogii, and S. minutisporum, cause human infections. Thailand is a popular travel destination in the world, with many attractions present in densely populated areas; thus, large numbers of people may be exposed to pathogens present in these areas. We conducted a comprehensive survey of Scedosporium species in 350 soil samples obtained from 35 sites of high human population density and tourist popularity distributed over 23 provinces and six geographic regions of Thailand. Soil suspensions of each sample were inoculated on three plates of Scedo-Select III medium to isolate Scedosporium species. In total, 191 Scedosporium colonies were isolated from four provinces. The species were then identified using PCR and sequencing of the beta-tubulin (BT2) gene. Of the 191 isolates, 188 were S. apiospermum, one was S. dehoogii, and species of two could not be exactly identified. Genetic diversity analysis revealed high haplotype diversity of S. apiospermum. Soil is a major ecological niche for Scedosporium and may contain S. apiospermum populations with high genetic diversity. This study of Scedosporium distribution might encourage health care providers to consider Scedosporium infection in their patients. [ABSTRACT FROM AUTHOR]

Scedosporium apiospermum and Lomentospora prolificans are important fungal species isolated from immunocompromised patients. Previous studies have demonstrated that these filamentous fungi exist as saprophytes in the soil and showed the highest minimum inhibitory concentration to several drugs. We aimed to examine how UVC affects the S. apiospermum and L. prolificans by investigating the role of UVC on growth, induction of apoptosis by ethidium bromide (EB)/acridine orange (AO) staining, and transcriptomic study of caspase recruitment domain family, member 9 (CARD-9) gene. Our studies showed that 15 minutes of exposure to UVC light effectively increased reduction in both organisms and caused changes in colony morphology, color, and hyphal growth pattern. After 15 min of UVC irradiation, apoptotic cells were quantitated by EB/AO staining, and the percentage of apoptosis was 96.06% in S. apiospermum and 28.30% in L. prolificans. CARD-9 gene expression results confirmed that apoptosis was induced in S. apiospermum and L. prolificans after UVC treatment and that S. apiospermum showed a higher expression of apoptosis signaling than L. prolificans. Our study explored the effects of UVC in the inactivation of S. apiospermum and L. prolificans. We hope that our data is useful to other researchers in future studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Neurological melioidosis, caused by Burkholderiapseudomallei, can lead to the development of severe symptoms associated with the nervous system. However, the pathogenic mechanism through which this bacterium infects neuronal cells has not been studied. This study showed that B. pseudomallei can infect human neuronal SH-SY5Y cells in vitro. Cycle-inhibiting factor (Cif), a type III secreted effector, is one of the virulence factors produced by B. pseudomallei upon infection. The B. pseudomallei cif-deleted mutant reduced the ability to invade neuronal cells compared with the parental strain. Our finding indicates that Cif is associated with B. pseudomallei invasion of human neuronal cells. Burkholderia pseudomallei is a pathogenic bacterium that causes human melioidosis, which is associated with a high mortality rate. However, the underlying mechanisms of B. pseudomallei pathogenesis are largely unknown. In this study, we examined the infection of human neuronal SH-Sy5y cells by several clinically relevant B. pseudomallei strains. We found that all tested B. pseudomallei strains can invade SH-Sy5y cells, undergo intracellular replication, cause actin-tail formation, and form multinucleated giant cells. Additionally, a deletion mutant of B. pseudomallei cycle-inhibiting factor (cif) was constructed that exhibited reduced invasion in SH-Sy5y cells. Complementation of cif restored invasion of the B. pseudomallei cif-deleted mutant. Our findings enhance understanding of B. pseudomallei pathogenicity in terms of the virulence factor Cif and demonstrate the function of Cif in neurological melioidosis. This may eventually lead to the discovery of novel targets for treatment and a strategy to control the disease. [ABSTRACT FROM AUTHOR]

The Scedosporium apiospermum species complex, comprising filamentous fungal species S. apiospermum sensu stricto, S. boydii, S. aurantiacum, S. dehoogii and S. minutispora, are important pathogens that cause a wide variety of infections. Although some species (S. boydii and S. apiospermum) have been isolated from patients in Thailand, no environmental surveys of these fungi have been performed in Thailand or surrounding countries. In this study, we isolated and identified species of these fungi from 68 soil and 16 water samples randomly collected from 10 parks in Bangkok. After filtration and subsequent inoculation of samples on Scedo-Select III medium, colony morphological examinations and microscopic observations were performed. Scedosporium species were isolated from soil in 8 of the 10 parks, but were only detected in one water sample. Colony morphologies of isolates from 41 of 68 soil samples (60.29%) and 1 of 15 water samples (6.67%) were consistent with that of the S. apiospermum species complex. Each morphological type was selected for species identification based on DNA sequencing and phylogenetic analysis of the β-tubulin gene. Three species of the S. apiospermum species complex were identified: S. apiospermum (71 isolates), S. aurantiacum (6 isolates) and S. dehoogii (5 isolates). In addition, 16 sequences could not be assigned to an exact Scedosporium species. According to our environmental survey, the S. apiospermum species complex is widespread in soil in Bangkok, Thailand. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei—a causative agent of melioidosis that is endemic in Southeast Asia and Northern Australia—is a Gram-negative bacterium transmitted to humans via inhalation, inoculation through skin abrasions, and ingestion. Melioidosis causes a range of clinical presentations including skin infection, pneumonia, and septicemia. Despite skin infection being one of the clinical symptoms of melioidosis, the pathogenesis of B. pseudomallei in skin fibroblasts has not yet been elucidated. In this study, we investigated B. pseudomallei pathogenesis in the HFF-1 human skin fibroblasts. On the basis of co-culture assays between different B. pseudomallei clinical strains and the HFF-1 human skin fibroblasts, we found that all B. pseudomallei strains have the ability to mediate invasion, intracellular replication, and multinucleated giant cell (MNGC) formation. Furthermore, all strains showed a significant increase in cytotoxicity in human fibroblasts, which coincides with the augmented expression of matrix metalloproteinase-2. Using B. pseudomallei mutants, we showed that the B. pseudomallei Bsa type III secretion system (T3SS) contributes to skin fibroblast pathogenesis, but O-polysaccharide, capsular polysaccharide, and short-chain dehydrogenase metabolism do not play a role in this process. Taken together, our findings reveal a probable connection for the Bsa T3SS in B. pseudomallei infection of skin fibroblasts, and this may be linked to the pathogenesis of cutaneous melioidosis. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis and scedosporiosis are life-threatening fungal infections with similar clinical manifestations in immunocompromised patients. Contrarily, Scedosporium apiospermum is susceptible to some azole derivative but often resistant to amphotericin B. Histopathological examination alone cannot diagnose these two fungal species. Pathogenesis studies could contribute to explore candidate protein markers for new diagnosis and treatment methods leading to a decrease in mortality. In the present study, proteomics was conducted to identify significantly altered proteins in A549 cells infected with or without Aspergillus fumigatus and S. apiospermum as measured at initial invasion. Protein validation was performed with immunogold labelling alongside immunohistochemical techniques in infected A549 cells and lungs from murine models. Further, cytokine production was measured, using the Bio-Plex-Multiplex immunoassay. The cytoskeletal proteins HSPA9, PA2G4, VAT1, PSMA2, PEX1, PTGES3, KRT1, KRT9, CLIP1 and CLEC20A were mainly changed during A. fumigatus infection, while the immunologically activated proteins WNT7A, GAPDH and ANXA2 were principally altered during S. apiospermum infection. These proteins are involved in fungal internalisation and structural destruction leading to pulmonary disorders. Interleukin (IL)-21, IL-1α, IL-22, IL-2, IL-8, IL-12, IL-17A, interferon-γ and tumour necrosis factor-α were upregulated in both aspergillosis and scedosporiosis, although more predominately in the latter, in accordance with chitin synthase-1 and matrix metalloproteinase levels. Our results demonstrated that during invasion, A. fumigatus primarily altered host cellular integrity, whereas S. apiospermum chiefly induced and extensively modulated host immune responses. [ABSTRACT FROM AUTHOR]

Psoriasis is mainly caused because of inappropriate immune responses in the epidermis. Rice (Oryza sativa L.: SRNC05053-6-2) consists of anthocyanin, which exhibits strong antioxidative and anti-inflammatory properties. This study aimed to evaluate the role of this black-coloured rice crude extract in alleviating the symptoms of psoriasis using human psoriatic artificial skin and an imiquimod-induced rat psoriasis model. Psoriasis-related genes, cytokines and chemokines were examined; in addition, the antioxidative and anti-inflammatory properties and the immunohistopathological features of this condition were studied. The results showed that the rice extract reduced the severity of psoriasis by (1) decreasing the epidermal thickness, acanthosis, hyperkeratosis, epidermal inflammation and degree of apoptosis induction via caspase-3, (2) increasing the expression levels of anti-inflammatory cytokines (IL-10 and TGF-β), (3) reducing the levels of pro-inflammatory cytokines (IL-6, IL-8, IL-20, IL-22 and TNF-α), chemokines (CCL-20) and anti-microbial peptides (psoriasin and β-defensin), (4) enhancing the antioxidative property (Nrf-2), (5) downregulating the levels of psoriasis-associated genes (psoriasin, β-defensin, koebnerisin 15L and koebnerisin 15S) and (6) upregulating the levels of psoriasis-improving genes (caspase-14, involucrin and filaggrin). Thus, the extract appears to exert therapeutic effects on psoriasis through its antioxidative and immunomodulatory properties. [ABSTRACT FROM AUTHOR]