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Journal of Fungi (Basel, Switzerland) Feb 2019Onychomycosis is mainly caused by two dermatophyte species, and . A study of nail invasion mechanisms revealed that the secreted subtilisin Sub6, which has never been... (Review)
Review
Onychomycosis is mainly caused by two dermatophyte species, and . A study of nail invasion mechanisms revealed that the secreted subtilisin Sub6, which has never been detected under in vitro growth conditions, was the main protease secreted by and during infection. In contrast, most of the proteases secreted during the digestion of keratin in vitro were not detected in infected nails. The hypothesis that proteases isolated from dermatophytes grown in a keratin medium are virulence factors is no longer supported. Non-dermatophyte fungi can also be infectious agents in nails. It is necessary to identify the infectious fungus in onychomycosis to prescribe adequate treatment, as moulds such as spp. and spp. are insensitive to standard treatments with terbinafine or itraconazole, which are usually applied for dermatophytes. In these refractory cases, topical amphotericin B treatment has shown to be effective. Terbinafine treatment failure against dermatophytes is also possible, and is usually due to resistance caused by a missense mutation in the squalene epoxidase enzyme targeted by the drug. resistance to terbinafine treatment is an emerging problem, and a switch to azole-based treatment may be necessary to cure such cases of onychomycosis.
PubMed: 30813287
DOI: 10.3390/jof5010020 -
Journal of Clinical Microbiology Aug 2023Dermatophytes are common causes of skin, hair, and nail infections in humans. The most common species causing infections in humans are Trichophyton rubrum, Trichophyton...
Dermatophytes are common causes of skin, hair, and nail infections in humans. The most common species causing infections in humans are Trichophyton rubrum, Trichophyton mentagrophytes, and Trichophyton interdigitale. Outbreaks of recalcitrant dermatophytosis have been reported in parts of South Asia, including those caused by a hypervirulent and resistant species, Trichophyton indotineae. We evaluated the antifungal susceptibility profiles of dermatophytes received by our laboratory from institutions across North America between 2021 and 2022 and performed species identification for isolates deemed to demonstrate resistance. Susceptibility testing was performed by CLSI broth microdilution methods, and species identification was performed by DNA sequence analysis. During this 2-year period, 271 dermatophyte isolates were included, the majority of which demonstrated low MIC values for terbinafine (geometric mean [GM] and modal MIC, 0.031 μg/mL and 0.008 μg/mL, respectively) and the azoles itraconazole, posaconazole, and voriconazole (0.035 to 0.049 μg/mL and ≤0.03 μg/mL). However, 18.6% of the isolates tested were resistant to terbinafine (MIC ≥ 0.5 μg/mL), including 21 T. rubrum and 21 T. indotineae isolates. These isolates were received from several different states in the United States and two provinces in Canada. In contrast, resistance to itraconazole was relatively rare. We also searched our laboratory database for earlier isolates that were resistant to terbinafine and identified 3 additional T. indotineae isolates, the earliest of which was from 2017. These results demonstrate that terbinafine resistance in dermatophytes was relatively common over this 2-year period and that T. indotineae is present in multiple areas in North America. Continued surveillance is warranted.
Topics: Humans; Terbinafine; Trichophyton; Itraconazole; Arthrodermataceae; Microbial Sensitivity Tests; Antifungal Agents; North America; Drug Resistance, Fungal
PubMed: 37432126
DOI: 10.1128/jcm.00562-23 -
Life (Basel, Switzerland) Dec 2023The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a... (Review)
Review
The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as and . Importantly, the new subspecies, known as , has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections.
PubMed: 38276250
DOI: 10.3390/life14010001 -
Microbial Genomics Nov 2021The medically relevant species complex has a variety of phenotypic presentations but shows relatively little genetic differences. Conventional barcodes, such as the...
The medically relevant species complex has a variety of phenotypic presentations but shows relatively little genetic differences. Conventional barcodes, such as the internal transcribed spacer (ITS) region or the beta-tubulin gene, are not able to completely resolve the relationships between these closely related taxa. , and are currently accepted as separate species. However, the status of certain variants, including the morphotypes and and the morphotype , remains to be deciphered. We conducted the first phylogenomic analysis of the species complex by studying 3105 core genes of 18 new strains from the BCCM/IHEM culture collection and nine publicly available genomes. Our analyses revealed a highly resolved phylogenomic tree with six separate clades. , and were confirmed in their status of species. The morphotypes and all grouped in their own respective clade with high support, suggesting that these morphotypes should be reinstituted to the species-level. Robinson-Foulds distance analyses showed that a combination of two markers (a ubiquitin-protein transferase and a MYB DNA-binding domain-containing protein) can mirror the phylogeny obtained using genomic data, and thus represent potential new markers to accurately distinguish the species belonging to the complex.
Topics: Arthrodermataceae; Phylogeny; Trichophyton
PubMed: 34730487
DOI: 10.1099/mgen.0.000707 -
BMC Genomics Jan 2022Circular RNAs (circRNAs) are a group of noncoding RNAs that participate in gene expression regulation in various pathways. The essential roles of circRNAs have been...
BACKGROUND
Circular RNAs (circRNAs) are a group of noncoding RNAs that participate in gene expression regulation in various pathways. The essential roles of circRNAs have been revealed in many species. However, knowledge of circRNAs in fungi is still not comprehensive.
RESULTS
Trichophyton rubrum (T. rubrum) is considered a model organism of human pathogenic filamentous fungi and dermatophytes. In this study, we performed a genome-wide investigation of circRNAs in T. rubrum based on high-throughput sequencing and ultimately identified 4254 circRNAs. Most of these circRNAs were specific to the conidial or mycelial stage, revealing a developmental stage-specific expression pattern. In addition, 940 circRNAs were significantly differentially expressed between the conidial and mycelial stages. PCR experiments conducted on seven randomly selected differentially expressed (DE-) circRNAs confirmed the circularized structures and relative expression levels of these circRNAs. Based on their genome locations, most circRNAs originated from intergenic regions, unlike those in plants and animals. Furthermore, we constructed circRNA-miRNA-mRNA regulatory networks that included 661 DE-circRNAs targeting 140 miRNAs and further regulating 2753 mRNAs. The relative expression levels of two randomly selected circRNA-miRNA-mRNA axes were investigated by qRT-PCR, and the competing endogenous RNA (ceRNA) network theory was validated. Functional enrichment analysis of the target genes suggested that they were significantly involved in posttranscriptional processes and protein synthesis as well as some small-molecule metabolism processes. CircRNAs are relatively more conserved in closely related dermatophytes but rarely conserved in distantly related species. Tru_circ07138_001 is a highly conserved circRNA that was conserved in all ten dermatophytes analyzed in our study and three distantly related species. Its host gene TERG_07138 was also highly conserved in two of these distantly related species Gallus gallus and Caenorhabditis elegans. The specific role of this circRNA deserves further exploration.
CONCLUSIONS
Our study is the first to provide a global profile of circRNAs in T. rubrum as well as dermatophytes. These results could serve as valuable resources for research on circRNA regulatory mechanisms in fungi and reveal new insights for further investigation of the physical characteristics of these significant human fungal pathogens.
Topics: Animals; Arthrodermataceae; Gene Expression Profiling; Gene Regulatory Networks; Humans; MicroRNAs; RNA, Circular; Spores, Fungal
PubMed: 34983376
DOI: 10.1186/s12864-021-08184-y -
Journal of Fungi (Basel, Switzerland) Aug 2015Since the early 20th century, onychomycosis originated with the onset of war, the use of occlusive footwear, and the mass migration of people by transportation in the... (Review)
Review
Since the early 20th century, onychomycosis originated with the onset of war, the use of occlusive footwear, and the mass migration of people by transportation in the United States. Even though onychomycosis has a high prevalence in the US, other parts of the world including Canada, West Africa, Southeast Asia, Northern Australia, and Europe have been well documented with cases of fungal toenail infection in their environments. () is the major dermatophyte responsible for toenail fungal infection and is typically diagnosed in conjunction with tinea pedis, especially in individuals older than 60 years. Gender roles, age, cultural habits, shoe gear, sports activities, and genetic predisposition all contribute to the different presentation of onychomycosis in these areas where organisms like dermatophytes, candida, and molds were isolated in a variety of cases. Despite the differences in isolated pathogens, treatment outcomes remained consistent. This literature review discusses the influence of tinea pedis, genetics, shoe gear, sports, and age on the development of onychomycosis.
PubMed: 29376909
DOI: 10.3390/jof1020211 -
British Medical Journal Jul 1968Fourteen cases are described in which the local application of corticosteroid preparations to ringworm infections of the skin have resulted in unusual clinical pictures....
Fourteen cases are described in which the local application of corticosteroid preparations to ringworm infections of the skin have resulted in unusual clinical pictures. A kerion-like lesion due to Trichophyton rubrum, intertriginous infections simulating candidiasis and due to Epidermophyton floccosum, and pictures resembling poikiloderma, papular rosacea, and indeterminate leprosy are among the changes that were seen in these patients.
Topics: Adolescent; Adult; Aged; Betamethasone; Diagnosis, Differential; Eczema; Epidermophyton; Female; Fluocinolone Acetonide; Glucocorticoids; Griseofulvin; Humans; Keratins; Male; Middle Aged; Skin Diseases; Tinea; Triamcinolone Acetonide; Trichophyton; Valerates
PubMed: 5662546
DOI: 10.1136/bmj.3.5611.149 -
MethodsX 2022and are the main causative pathogens of onychomycosis. However, the sensitivity and specificity of conventional microscopic tests are insufficient for reliable...
and are the main causative pathogens of onychomycosis. However, the sensitivity and specificity of conventional microscopic tests are insufficient for reliable diagnoses of onychomycosis. In this study, we developed loop-mediated isothermal amplification (LAMP) assays for the rapid and specific identification of the two major spp. We designed LAMP primers targeting the internal transcribed spacer 1 region of the and . Through rigorous optimization of the reaction conditions, we defined a universal reaction condition for both LAMP assays.
PubMed: 36353357
DOI: 10.1016/j.mex.2022.101891 -
Virulence 2015
Topics: Animals; Disease Models, Animal; Humans; Mice; Tinea; Trichophyton
PubMed: 26065321
DOI: 10.1080/21505594.2015.1027480 -
Medical Mycology Journal 2021Terbinafine (TRF)-resistant Trichophyton interdigitale and Trichophyton rubrum have been isolated from human patients. These strains have missense mutations...
Terbinafine (TRF)-resistant Trichophyton interdigitale and Trichophyton rubrum have been isolated from human patients. These strains have missense mutations (Leu393Ser/Phe or Phe397Leu) in the squalene epoxidase-encoding gene, SQLE. We developed a PCR detection method to identify hotspot mutation sites in SQLE genes of dermatophytes. To sequence hotspots in isolates, we prepared primers based on conserved sequences of T. rubrum and T. interdigitale SQLEs. Approximately 390-bp long DNA bands for T. rubrum, T. interdigitale, and Trichophyton indotineae strains were sequenced. Hotspots were detected only in TRF-resistant strains. This PCR-based method is simpler and more rapid than the conventional test.
Topics: Antifungal Agents; Arthrodermataceae; Drug Resistance, Fungal; Humans; Microbial Sensitivity Tests; Terbinafine; Trichophyton
PubMed: 34053979
DOI: 10.3314/mmj.21-00001