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Diversity of phenotypically non-dermatophyte, non-Aspergillus filamentous fungi causing nail infections: importance of accurate identification and antifungal susceptibility testing.

ABSTRACT: Onychomycosis is most commonly caused by dermatophytes. In this study, we examined the spectrum of phenotypically non-dermatophyte and non-Aspergillus fungal isolates recovered over a 10-year period from nails of patients with onychomycosis in Hong Kong. A total of 24 non-duplicated isolates recovered from 24 patients were included. The median age of the patients was 51 years, and two-thirds of them were males. One-third and two-thirds had finger and toe nail infections respectively. Among these 24 nail isolates, 17 were confidently identified as 13 different known fungal species, using a polyphasic approach. These 13 species belonged to 11 genera and ?9 families. For the remaining seven isolates, multilocus sequencing did not reveal their definite species identities. These seven potentially novel species belonged to four different known and three potentially novel genera of seven families. 33.3%, 41.7% and 95.8% of the 24 fungal isolates possessed minimum inhibitory concentrations of >1?µg/mL to terbinafine, itraconazole and fluconazole, respectively, the first line treatment of onychomycosis. A high diversity of moulds was associated with onychomycosis. A significant proportion of the isolates were potentially novel fungal species. To guide proper treatment, molecular identification and antifungal susceptibility testing should be performed for these uncommonly isolated fungal species.

SUBMITTER: Tsang CC

PROVIDER: S-EPMC6455232 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Diversity of phenotypically non-dermatophyte, non-Aspergillus filamentous fungi causing nail infections: importance of accurate identification and antifungal susceptibility testing.

Tsang Chi-Ching CC Tang James Y M JYM Chan Ka-Fai KF Lee Chun-Yi CY Chan Jasper F W JFW Ngan Antonio H Y AHY Cheung Mei M Lau Eunice C L ECL Li Xin X Ng Ricky H Y RHY Lai Christopher K C CKC Fung Kitty S C KSC Lau Susanna K P SKP Woo Patrick C Y PCY

Emerging microbes & infections 20190101 1

Onychomycosis is most commonly caused by dermatophytes. In this study, we examined the spectrum of phenotypically non-dermatophyte and non-Aspergillus fungal isolates recovered over a 10-year period from nails of patients with onychomycosis in Hong Kong. A total of 24 non-duplicated isolates recovered from 24 patients were included. The median age of the patients was 51 years, and two-thirds of them were males. One-third and two-thirds had finger and toe nail infections respectively. Among these ...[more]

PMID: 30938262

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Project description:Background:Dermatophytosis represents one of the common infectious diseases worldwide and it is a major public health problem around the globe. The disease causes considerable morbidity and still continues to increase especially in developing countries. Objective:This study was undertaken to determine the prevalence of dermatophytes and the spectrum of fungal agents in patients attending Rank Higher Specialized Dermatology Clinic. Methods:A cross-sectional study has been conducted, in which 318 samples from 318 suspected patients were collected. Samples include hair, nail, and skin. A portion of each sample was examined microscopically and the remaining portion of each sample was cultured onto plates of Sabouraud's dextrose agar containing chloramphenicol with and without cycloheximide. Isolates were identified by studying the macroscopic and microscopic characteristics of the colonies. Results:Tinea capitis was the predominant clinical manifestation accounting for 53.4% of the cases. Patients with age group 1-14 years were more affected. Of 318 samples, fungi were detected in 133 (54.4%) by direct wet mount while 148/315 (46.5%) of them were culture positive. From these 72/148 (46.8%) were dermatophytes. T. tonsurans was the most common pathogen in tinea capitis, whereas T. mentagrophytes was the most common pathogen in tinea corporis. Among dermatophyte isolates, T. tonsurans 29/72 (40.2%) was the most common cause of infection. Among non-dermatophyte molds, Cladosporiumspp. 21/63 (33.3%) was predominant isolate followed by Neoscytalidim dimidatum 11/63 (17.4%) and Alternariaspp. 9/63 (14.2%), respectively. Yeasts also account for 13 (8.7%) of the total suspects of dermatophytosis. Conclusion:In this study, the prevalence of dermatophytes was higher in tinea capitis 46/72 (63.8%) and T. tonsurans 29/72 (40%) was the dominant-isolated dermatophyte. Recovery of a large number of dermatophytes and non-dermatophyte fungi in our study showed that non-dermatophyte fungi are emerging as important causes of dermatophytosis warranting further intensive epidemiological studies that have public health significance are needed.

Project description:The cell wall integrity signaling (CWIS) pathway is involved in fungal cell wall biogenesis. This pathway is composed of sensor proteins, protein kinase C (PKC), and the mitogen-activated protein kinase (MAPK) pathway, and it controls the transcription of many cell wall-related genes. PKC plays a pivotal role in this pathway; deficiencies in PkcA in the model filamentous fungus Aspergillus nidulans and in MgPkc1p in the rice blast fungus Magnaporthe grisea are lethal. This suggests that PKC in filamentous fungi is a potential target for antifungal agents. In the present study, to search for MgPkc1p inhibitors, we carried out in silico screening by three-dimensional (3D) structural modeling and performed growth inhibition tests for M. grisea on agar plates. From approximately 800,000 candidate compounds, we selected Z-705 and evaluated its inhibitory activity against chimeric PKC expressed in Saccharomyces cerevisiae cells in which the kinase domain of native S. cerevisiae PKC was replaced with those of PKCs of filamentous fungi. Transcriptional analysis of MLP1, which encodes a downstream factor of PKC in S. cerevisiae, and phosphorylation analysis of the mitogen-activated protein kinase (MAPK) Mpk1p, which is activated downstream of PKC, revealed that Z-705 specifically inhibited PKCs of filamentous fungi. Moreover, the inhibitory activity of Z-705 was similar to that of a well-known PKC inhibitor, staurosporine. Interestingly, Z-705 inhibited melanization induced by cell wall stress in M. grisea We discuss the relationships between PKC and melanin biosynthesis.IMPORTANCE A candidate inhibitor of filamentous fungal protein kinase C (PKC), Z-705, was identified by in silico screening. A screening system to evaluate the effects of fungal PKC inhibitors was constructed in Saccharomyces cerevisiae Using this system, we found that Z-705 is highly selective for filamentous fungal PKC in comparison with S. cerevisiae PKC. Analysis of the AGS1 mRNA level, which is regulated by Mps1p mitogen-activated protein kinase (MAPK) via PKC, in the rice blast fungus Magnaporthe grisea revealed that Z-705 had a PKC inhibitory effect comparable to that of staurosporine. Micafungin induced hyphal melanization in M. grisea, and this melanization, which is required for pathogenicity of M. grisea, was inhibited by PKC inhibition by both Z-705 and staurosporine. The mRNA levels of 4HNR, 3HNR, and SCD1, which are essential for melanization in M. grisea, were suppressed by both PKC inhibitors.

Project description:Antimicrobial peptides (AMPs) are ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. The search for new AMPs has increased in recent years, due to the growing development of microbial resistance to therapeutical drugs. In this work, we evaluate the effects of Tityus serrulatus venom (Tsv), its fractions and its major toxin Ts1, a beta-neurotoxin, on fungi growth. The fractions were obtained by ion-exchange chromatography of Tsv. The growth inhibition of 11 pathogenic and non-pathogenic filamentous fungi (Aspergillus fumigatus, A. nidulans, A. niger, A. terreus, Neurospora crassa, Penicillium corylophilum, P. ochrochloron, P. verrucosum, P. viridicatum, P. waksmanii, and Talaromyces flavus) was evaluated by quantitative microplate reader assay. Tsv (100 and 500 ?g/well, which correspond to 1 and 5 mg/mL, respectively, of total soluble protein) was active in inhibiting growth of A. nidulans, A. terreus, P. corylophilum, and P. verrucosum, especially in the higher concentration used and at the first 30 h. After this period, fungi might have used Tsv components as alternative sources of nutrients, and therefore, increased their growth tax. Only fractions IX, X, XI, XIIA, XIIB (3 and 7.5 ?g/well, which correspond to 30 and 75 ?g/mL, respectively, of total soluble protein) and Ts1 (1.5, 3, and 6 ?g/well, which correspond to 2.18, 4.36, and 8.72 ?M, respectively) showed antifungal activity. Ts1 showed to be a non-morphogenic toxin with dose-dependent activity against A. nidulans, inhibiting 100% of fungal growth from 3 ?g/well (4.36 ?M). The inhibitory effect of Ts1 against A. nidulans growth was accompanied by fungistatic effects and was not amended by 1 mM CaCl2 or tetrodotoxin (46.98 and 93.96 ?M). The structural differences between Ts1 and drosomycin, a potent cysteine-rich antifungal peptide, are discussed here. Our results highlight the antifungal potential of the first cysteine-containing scorpion toxin. Since Ts1 is a multifunctional toxin, we suggest that it could be used as a template in the design of engineered scorpion AMPs and in the search for new mechanisms of action of antifungal drugs.

Dataset Information

Diversity of phenotypically non-dermatophyte, non-Aspergillus filamentous fungi causing nail infections: importance of accurate identification and antifungal susceptibility testing.

Publications

Diversity of phenotypically non-dermatophyte, non-Aspergillus filamentous fungi causing nail infections: importance of accurate identification and antifungal susceptibility testing.

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