Chromoblastomycosis is a chronic, progressive subcutaneous mycosis that is endemic in tropical and subtropical countries. Cladophialophora carrionii and Fonsecaea pedrosoi are prevalent etiological agents. The potential role of the proteolytic activity of extracellular enzymes in these fungi and its relationship with the pathogenesis of the disease has not been proven. Some phenotypic traits have been associated with the virulence of other fungi; i.e., their different rate of protease, phospholipase, and esterase excretion, melanin, and thermotolerance. The aim of this study was the identification of extracellular enzymes that could be considered virulence markers of chromoblastomycosis agents. Therefore, we tested 29 C. carrionii and 11 F. pedrosoi clinical isolates to determine their hydrolytic and physiologic characteristics. All the tested isolates grew at a range of 30°-37 °C; except 2 strains of F. pedrosoi that grew slowly at 40 °C. We noticed that the hydrolytic capabilities of the tested isolates were positive for urea hydrolysis in almost all, while both strains were negative for DNase, hemolysin, and gelatin. C. carrionii and F. pedrosoi had phospholipase and esterase activity. These findings were similar for most isolates. All strains showed an association between phospholipase activity and moderate to severe lesions. However, only in F. pedrosoi isolates, the association remains significant. We conclude that the different enzymatic production reported here may be linked to the clinical manifestations of these pathologies. Notwithstanding, the influence of other virulence factors is not excluded.

BACKGROUND: Superficial fungal infections are often seen in day-to-day clinical practice, and their prevalence continues to rise worldwide. Over the years, a change in the pattern of dermatophytoses has been noted.
OBJECTIVE: This study aimed to determine the epidemiologic profile of dermatophytes at the Department of Dermatology, University Hospital Jena, from 2007 to 2013.
METHODS: The retrospective study was carried out with a total of 4556 samples collected from 3607 patients suspected of superficial fungal infections during the 7-year study period.
RESULTS: Among the 3607 suspected patients, 1951 (54.09%) were men and 1656 (45.91%) were women. Of 4556 samples, 703 (15.43%) samples were positive for fungal culture, which included 585 (83.21%) dermatophytes and 118 (16.79%) non-dermatophytes. Trichophyton (T.) rubrum was the most common isolated pathogen in 73.33% of the dermatophyte cases. Among dermatophyte-infected patients, men were most likely to be affected (63.48%) as well as those of higher age (61 to 80). The most commonly affected areas were nails (33.16%) and feet (33%). T rubrum was recurrently isolated in several regions with exception of the scalp where M canis (58.33%) was the most frequently isolated pathogen. About 16.04% of cases had a history of treatment taken prior to sampling. The majority of the affected individuals did not have any prior animal contact (77.26%). T benhamiae was exclusively associated with contact to guinea pigs.
CONCLUSIONS: Trichophyton rubrum was the most frequently isolated pathogen in several regions except the scalp. New dermatophyte species emerged with time especially T benhamiae.

A series of indole-derived methoxylated chalcones were described as anti-dermatophyte agents. The in vitro antifungal susceptibility testing against different dermatophytes revealed that most of compounds had potent activity against the dermatophyte strains. In particular, the 4-ethoxy derivative 4d with MIC values of 0.25-2 μg/ml was the most potent compound against Trichophyton interdigitale, Trichophyton veruccosum and Microsporum fulvum. Moreover, the 4-butoxy analog 4i displaying MIC values in the range of 1-16 μg/ml had the highest inhibitory activity against Trichophyton mentagrophytes, Microsporum canis, and Arthroderma benhamiae. To predict whether the synthesized compounds interact with tubulin binding site of dermatophytes, the 3D-structure of target protein was modeled by homology modeling and then used for molecular docking and molecular dynamics (MD) simulation studies. Docking simulation revealed that the promising compound 4d can properly bind with tubulin. The molecular dynamics analysis showed that interactions of compound 4d with the active site of target protein have binding stability throughout MD simulation. The results of this study could utilize in the design of more effective antifungal drugs with tubulin inhibition mechanism against keratinophilic fungi.

BACKGROUND: The aggressive and timely treatment of post-traumatic fungal infections is the most efficacious way to reduce morbidity and mortality. Compared to the military trauma population, studies reporting on fungal infections in civilian trauma are not well described. The purpose of this study was to describe characteristics of civilian trauma patients who developed fungal infections and to identify common risk factors and report any delays between injury and treatment.
METHODS: This was a five-year (1/1/2013-3/1/2018) retrospective, descriptive study across six level 1 trauma centers. All consecutively admitted trauma patients (≥18 years) with laboratory-confirmed fungal wound infections were included. Patients with solely candida wound isolates were excluded. Patient demographics, clinical wound and infection characteristics, organisms cultured, treatment modalities, length of stay, in-hospital mortality, and any diagnostic or treatment delays were described.
RESULTS: Of the 54,521 trauma patients screened for fungal infection, 12 were identified. All patients suffered major injuries after blunt trauma (abbreviated injury score 3-5) and sustained wound contamination, and in nine patients, the cause of injury was motor vehicle. Six had open wounds/fractures on admission. The geographical region with the highest rate of fungal infection was Texas (n = 7), followed by Kansas (N = 3), then Missouri (N = 2). First symptoms of infection (leukocytosis or fever (n = 10)) presented a median of 6.3 (4.1-9.8) days after injury. Wound management entailed a combination of debridements (n = 8), negative pressure wound therapy (n = 9), amputation (n = 6), and antifungal treatment (n = 10). All fungal isolates identified from the wound site were hyphomycetes. A median of 2.1 (1.8-4.0) days passed from diagnosis to first antifungal treatment, and 3 patients died.
CONCLUSIONS: Our study shows the challenges surrounding diagnosis and treatment of fungal infections secondary to trauma. Non-specific fungal infection symptoms, such as leukocytosis and fever, typically presented a week after injury. Vigilance for investigating risk factors and infection symptoms may help clinicians with more timely management of trauma patients with a severe fungal infection.

Dermatophytosis is a superficial fungal infection of keratinized structures that exhibits an increasing prevalence in humans and is thus requesting novel prophylactic strategies and therapies. However, precise mechanisms used by dermatophytes to adhere at the surface of the human epidermis and invade its stratum corneum are still incompletely identified, as well as the responses provided by the underlying living keratinocytes during the infection. We hereby report development of an in vitro model of human dermatophytosis through infection of reconstructed human epidermis (RHE) by arthroconidia of the anthropophilic Trichophyton rubrum species or of the zoophilic Microsporum canis and Arthroderma benhamiae species. By modulating density of arthroconidia in the inoculum and duration of exposure to such pathogens, fungal infection limited to the stratum corneum was obtained, mimicking severe but typical in vivo situation. Fungal elements in infected RHE were monitored over time by histochemical analysis using periodic-acid Schiff-staining or quantified by qPCR-detection of fungal genes inside RHE lysates. This model brings improvements to available ones, dedicated to better understand how dermatophytes and epidermis interact, as well as to evaluate preventive and therapeutic agents. Indeed, miconazole topically added to RHE was demonstrated to inhibit fungal infection in this model.

Organic waste is a rich substrate for microbial growth, and because of that, workers from waste industry are at higher risk of exposure to bioaerosols. This study aimed to assess fungal contamination in two plants handling solid waste management. Air samples from the two plants were collected through an impaction method. Surface samples were also collected by swabbing surfaces of the same indoor sites. All collected samples were incubated at 27°C for 5 to 7 d. After lab processing and incubation of collected samples, quantitative and qualitative results were obtained with identification of the isolated fungal species. Air samples were also subjected to molecular methods by real-time polymerase chain reaction (RT PCR) using an impinger method to measure DNA of Aspergillus flavus complex and Stachybotrys chartarum. Assessment of particulate matter (PM) was also conducted with portable direct-reading equipment. Particles concentration measurement was performed at five different sizes (PM0.5; PM1; PM2.5; PM5; PM10). With respect to the waste sorting plant, three species more frequently isolated in air and surfaces were A. niger (73.9%; 66.1%), A. fumigatus (16%; 13.8%), and A. flavus (8.7%; 14.2%). In the incineration plant, the most prevalent species detected in air samples were Penicillium sp. (62.9%), A. fumigatus (18%), and A. flavus (6%), while the most frequently isolated in surface samples were Penicillium sp. (57.5%), A. fumigatus (22.3%) and A. niger (12.8%). Stachybotrys chartarum and other toxinogenic strains from A. flavus complex were not detected. The most common PM sizes obtained were the PM10 and PM5 (inhalable fraction). Since waste is the main internal fungal source in the analyzed settings, preventive and protective measures need to be maintained to avoid worker exposure to fungi and their metabolites.

A detailed comparative study on chemical and bioactive properties of wild and cultivated Ganoderma lucidum from Serbia (GS) and China (GCN) was performed. This species was chosen because of its worldwide use as medicinal mushroom. Higher amounts of sugars were found in GS, while higher amounts of organic acids were recorded in GCN. Unsaturated fatty acids predominated over saturated fatty acids. GCN revealed higher antioxidant activity, while GS exhibited inhibitory potential against human breast and cervical carcinoma cell lines. No cytotoxicity in non-tumour liver primary cell culture was observed for the different samples. Both samples possessed antibacterial and antifungal activities, in some cases even better than the standard antimicrobial drugs. This is the first study reporting a comparison of chemical compounds and bioactivity of G. lucidum samples from different origins.

Dendrodolides A-M (1-13), 13 new 12-membered macrolides, were isolated from Dendrodochium sp., a fungus associated with the sea cucumber Holothuria nobilis Selenka, which was collected from the South China Sea. The structures of the dendrodolides were elucidated by means of detailed spectroscopic analysis and X-ray single-crystal diffraction. The absolute configurations were assigned using the modified Mosher method, exciton-coupled circular dichroism (ECCD), electronic solution and solid-state circular dichroism (ECD) supported by time-dependent density functional theory (TDDFT) ECD calculations, and X-ray analysis. A detailed conformational analysis of the 13 derivatives indicated that the conformation of the flexible macrolide ring plays a decisive role in their chiroptical properties. Thus, it is highly recommended to apply advanced levels of theory and to avoid simple comparison of ECD spectra to determine the absolute configurations of these derivatives. In an in vitro bioassay, compounds 1-5, 7-9, 11, and 12 exhibited different levels of growth inhibitory activity against SMMC-7721 and HCT116 cells. This is the first report of 12-membered macrolides from the fungus of the genus Dendrodochium . The coisolation of four pairs of epimers is extremely interesting and indicates the complexity of β-ketoreductase stereospecificity in the biosynthesis of enigmatic iterative fungal polyketides.

Voriconazole is a first-line agent in the treatment of many invasive fungal infections and is known to display highly variable pharmacokinetics. Previous studies of voriconazole therapeutic drug monitoring (TDM) have suggested concentration monitoring to be clinically useful but have been limited by small patient samples at a single institution. This multicenter retrospective study aimed to investigate relationships between voriconazole concentration and clinical outcomes and adverse events and to assess clinical factors and drug interactions that may affect voriconazole concentration. Medical records were reviewed for patients who received voriconazole and had at least 1 concentration measured at seven hospitals in Australia. The study included 201 patients with 783 voriconazole trough concentrations. Voriconazole concentrations of <1.7 mg/liter were associated with a significantly greater incidence of treatment failure (19/74 patients [26%]) than concentrations of ≥1.7 mg/liter (6/89 patients [7%]) (P < 0.01). Neurotoxic adverse events (visual and auditory hallucinations) occurred more frequently at voriconazole concentrations of >5 mg/liter (10/31 patients [32%]) than at concentrations of ≤5 mg/liter (2/170 patients [1.2%]) (P < 0.01). Multiple regression analysis of voriconazole concentration identified associations between increasing patient weight, oral administration of voriconazole, and coadministration of phenytoin or rifampin and significantly reduced concentrations, and associations between increasing patient age and coadministration of proton pump inhibitors and increased concentrations. Coadministration of glucocorticoids was found to significantly reduce voriconazole concentrations, inferring a previously unreported drug interaction between glucocorticoids and voriconazole.

Sphaeropsidone and episphaeropsidone are two phytotoxic dimedone methyl ethers produced by Diplodia cupressi, the causal agent of a canker disease of cypress in the Mediterranean area. In this study, eight derivatives obtained by chemical modifications and two natural analogues were assayed for phytotoxic and antifungal activities, and a structure-activity relationship was examined. Each compound was tested on nonhost plants and on five fungal pathogenic species belonging to the genus Phytophthora. The results provide insights into structure-activity relationships within these compounds. It was found that the hydroxy group at C-5, the absolute C-5 configuration, the epoxy group, and the C-2 carbonyl group appear to be structural features important in conferring biological activity. The conversion of sphaeropsidone into the corresponding 1,4-dione derivative led to a compound showing greater antifungal activity than its precursor. This finding could be useful in devising new natural fungicides for practical application in agriculture.