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Frontiers in Microbiology 2019Dermatophytosis is a superficial fungal infection mostly restricted to keratinized tissues such as skin, hair, and nails but with potential to cause invasive or even...
Dermatophytosis is a superficial fungal infection mostly restricted to keratinized tissues such as skin, hair, and nails but with potential to cause invasive or even systemic disease in immunocompromised patients. is the main etiologic agent, accounting for approximately 80% of the cases. Mononuclear phagocytes respond to pathogens through phagocytosis followed by production of several antimicrobial molecules, such as reactive oxygen and nitrogen species, and failure in doing so may contribute to development of chronic fungal infections. Toll-like receptors (TLRs) located on the surface of phagocytic cells bind either directly to target particles or through opsonizing ligands and trigger an actin-mediated ingestion. Even though the mechanisms involved in TLR-mediated cytokine responses are well established, the contribution of TLR in the recognition of by adherent monocytes remains unclear. Here, we report that phagocytosis of conidia by adherent monocytes is mediated by TLR2. Blockade of TLR2 by neutralizing antibodies impaired the fungicidal activity of monocytes as well their secretion of tumor necrosis factor (TNF)-α, but neither nitric oxide (NO) production nor interleukin (IL)-10 secretion was disturbed. So far, our data suggest that TLR2 is required for efficient conidial phagocytosis, and the absence of TLR2 signaling in human monocytes may impair the subsequent inflammatory response. These findings expand our understanding of phagocyte modulation by this important fungal pathogen and may represent a potential target for interventions aiming at enhancing antifungal immune responses.
PubMed: 31824444
DOI: 10.3389/fmicb.2019.02589 -
Journal of Fungi (Basel, Switzerland) Nov 2022Onychomycosis is a fungal disease of the nail that is found worldwide and is difficult to diagnose accurately. This study used metagenomics to investigate the...
Onychomycosis is a fungal disease of the nail that is found worldwide and is difficult to diagnose accurately. This study used metagenomics to investigate the microbiology of 18 clinically diagnosed mycotic nails and two normal nails for fungi and bacteria using the ITS2 and 16S loci. Four mycotic nails were from Bass Coast, six from Melbourne Metropolitan and eight from Shepparton, Victoria, Australia. The mycotic nails were photographed and metagenomically analysed. The ITS2 sequences for and averaged over 90% of hits in 14/18 nails. The high abundance of sequences of a single dermatophyte, compared to all other fungi in a single nail, made it the most likely infecting agents (MLIA). and interdigitale/mentagrophytes were found in Bass Coast and Shepparton while only was found in Melbourne. Two nails with mixed with high abundance non-dermatophyte moulds (NDMs) (, ) were also observed. The two control nails contained chiefly and . For bacteria, was in every nail and was the most abundant, including the control nails, with an overall mean rate of 66.01%. , , and also featured.
PubMed: 36422019
DOI: 10.3390/jof8111198 -
Antimicrobial Agents and Chemotherapy Apr 2022The multi-antifungal drug-resistant strain (NUBS21012) of Trichophyton rubrum was isolated from a patient with recurrent tinea corporis. The resistant strain encoded Phe...
The multi-antifungal drug-resistant strain (NUBS21012) of Trichophyton rubrum was isolated from a patient with recurrent tinea corporis. The resistant strain encoded Phe at codon 393 instead of Leu (L393F) in the squalene epoxidase () gene. The expression of genes encoding ATP-binding cassette transporter proteins increased in the strain compared to that of other strains. This result provides evidence that ATP-binding cassette transporter proteins are closely associated with azole resistance.
Topics: ATP-Binding Cassette Transporters; Antifungal Agents; Arthrodermataceae; Drug Resistance, Fungal; Humans; Microbial Sensitivity Tests; Terbinafine; Trichophyton
PubMed: 35341316
DOI: 10.1128/aac.02393-21 -
Scientific Reports Jun 2022Trichophyton rubrum, a major human pathogenic dermatophyte, is responsible for the most recurrent dermatophytoses as globally important superficial fungal infections....
Trichophyton rubrum, a major human pathogenic dermatophyte, is responsible for the most recurrent dermatophytoses as globally important superficial fungal infections. Typical chemotherapy is used to handle such infections; however, emerging drug resistance and side effects necessitate the new remedial method development. Cold atmospheric plasma (CAP) is an emerging technology, consisted of neutral and charged particles and photons newly developed as a potent and safe antimicrobial technique to combat drug-resistant microbial pathogens. In the present study, the vast effects of CAP irradiation containing oxygen (2%) and helium (98%) on T. rubrum growth and pathogenicity were explored. After exposure of T. rubrum to CAP jet for 90, 120, 150, 180, and 210 s in 96-well microtiter plates, cell morphology and viability, ergosterol content of fungal hyphae, HSP90 gene expression, and the pattern of drug susceptibility were studied by using electron microscopy, RT-qPCR, spectrophotometry, disk diffusion and CLSI microbroth dilution methods. CAP irradiation significantly inhibited the fungal growth by 25.83 to 89.10%, reduced fungal cell viability by 11.68 to 87.71%, disrupted cellular membranous organelles and structures of the fungal hyphae, and suppressed efficiently the expression of HSP90 gene by 2 folds in 210 s exposure. Taken together, our results demonstrated that CAP is an efficient tool with potential in-vivo therapeutic applications against chronic dermatophytosis caused by T. rubrum due to its effectiveness, harmless, and ease of access.
Topics: Antifungal Agents; Arthrodermataceae; Gene Expression; HSP90 Heat-Shock Proteins; Plasma Gases
PubMed: 35676321
DOI: 10.1038/s41598-022-13828-4 -
Antimicrobial Agents and Chemotherapy May 2018Dermatophytosis, the commonest superficial fungal infection, has gained recent attention due to its change of epidemiology and treatment failures. Despite the...
Dermatophytosis, the commonest superficial fungal infection, has gained recent attention due to its change of epidemiology and treatment failures. Despite the availability of several agents effective against dermatophytes, the incidences of chronic infection, reinfection, and treatment failures are on the rise. and are the two species most frequently identified among clinical isolates in India. Consecutive patients ( = 195) with suspected dermatophytosis during the second half of 2014 were included in this study. Patients were categorized into relapse and new cases according to standard definitions. Antifungal susceptibility testing of the isolated species ( = 127) was carried out with 12 antifungal agents: fluconazole, voriconazole, itraconazole, ketoconazole, sertaconazole, clotrimazole, terbinafine, naftifine, amorolfine, ciclopirox olamine, griseofulvin, and luliconazole. The squalene epoxidase gene was evaluated for mutation (if any) in 15 and 5 isolates exhibiting high MICs for terbinafine. A T1189C mutation was observed in four and two isolates. This transition leads to the change of phenylalanine to leucine in the 397th position of the squalene epoxidase enzyme. In homology modeling the mutant residue was smaller than the wild type and positioned in the dominant site of squalene epoxidase during drug interaction, which may lead to a failure to block the ergosterol biosynthesis pathway by the antifungal drug.
Topics: Allylamine; Antifungal Agents; Arthrodermataceae; Ciclopirox; Drug Resistance, Fungal; Fluconazole; Itraconazole; Microbial Sensitivity Tests; Morpholines; Squalene Monooxygenase; Terbinafine; Trichophyton; Voriconazole
PubMed: 29530857
DOI: 10.1128/AAC.02522-17 -
Cell Death & Disease Jan 2021Technology of generating human epidermal derivatives with physiological relevance to in vivo epidermis is continuously investigated for improving their effects on...
Technology of generating human epidermal derivatives with physiological relevance to in vivo epidermis is continuously investigated for improving their effects on modeling of human natural dermatological status in basic and clinical studies. Here, we report a method of robust establishment and expansion of human primary epidermal organoids (hPEOs) under a chemically defined condition. hPEOs reconstruct morphological, molecular, and functional features of human epidermis and can expand for 6 weeks. Remarkably, hPEOs are permissive for dermatophyte infections caused by Trichophyton Rubrum (T. rubrum). The T. rubrum infections on hPEOs reflect many aspects of known clinical pathological reactions and reveal that the repression on IL-1 signaling may contribute to chronic and recurrent infections with the slight inflammation caused by T. rubrum in human skin. Thus, our present study provides a new insight into the pathogenesis of T. rubrum infections and indicates that hPEOs are a potential ex vivo model for both basic studies of skin diseases and clinical studies of testing potential antifungal drugs.
Topics: Adolescent; Adult; Arthrodermataceae; Cells, Cultured; Child; Dermatomycoses; Epidermal Cells; Epidermis; Humans; Middle Aged; Organoids; Young Adult
PubMed: 33414472
DOI: 10.1038/s41419-020-03330-y -
Journal of Fungi (Basel, Switzerland) Dec 2020is causing an increasing number of invasive infections, especially in immunocompromised and diabetic patients. The fungal invasive infectious process is complex and has...
is causing an increasing number of invasive infections, especially in immunocompromised and diabetic patients. The fungal invasive infectious process is complex and has not yet been fully elucidated. Therefore, this study aimed to understand the cellular and molecular mechanisms during the interaction of macrophages and . For this purpose, we used a co-culture of previously germinated and heat-inactivated conidia placed in contact with human macrophages cell line THP-1 for 24 h. This interaction led to a higher level of release of interleukins IL-6, IL-2, nuclear factor kappa beta (NF-κB) and an increase in reactive oxygen species (ROS) production, demonstrating the cellular defense by macrophages against dead fungal elements. Cell viability assays showed that 70% of macrophages remained viable during co-culture. Human microRNA expression is involved in fungal infection and may modulate the immune response. Thus, the macrophage expression profile of microRNAs during co-culture revealed the modulation of 83 microRNAs, with repression of 33 microRNAs and induction of 50 microRNAs. These data were analyzed using bioinformatics analysis programs and the modulation of the expression of some microRNAs was validated by qRT-PCR. In silico analysis showed that the target genes of these microRNAs are related to the inflammatory response, oxidative stress, apoptosis, drug resistance, and cell proliferation.
PubMed: 33322794
DOI: 10.3390/jof6040363 -
Frontiers in Microbiology 2022is the most pathogenic type of fungal skin infection. It often invades and grows in a keratin-rich matrix, and lesions include human skin, hair, and fingernails...
is the most pathogenic type of fungal skin infection. It often invades and grows in a keratin-rich matrix, and lesions include human skin, hair, and fingernails (toenails). We designed LAMP primers for and developed a LAMP-Microfluidic chip detection system for . This system detects six common species of in the genus , including , , , , , and . The specificity reached 100%, and the sensitivity could reach about 1 × 10 copies/μl. The entire detection process can be completed within 60 min and does not cross-react with other dermatophytes. The established LAMP-Microfluidic chip detection system has the advantages of simple operation, high specificity, and high sensitivity, and has the potential for clinical application.
PubMed: 36312927
DOI: 10.3389/fmicb.2022.1031388 -
Microbiology and Immunology Feb 2019Silkworm, Bombyx mori, has various advantages as an experimental animal, such as the low cost for rearing and fewer ethical problems. Models utilizing silkworms of... (Review)
Review
Silkworm, Bombyx mori, has various advantages as an experimental animal, such as the low cost for rearing and fewer ethical problems. Models utilizing silkworms of infection with pathogenic bacteria have been established for identification of genes encoding virulence factors by large-scale in vivo screening. In this review, we describe recent progress in the study of silkworm infection models for elucidating the mechanisms of fungi infection. Silkworm infection models have been established for Candida albicans, Candida tropicalis, Candida glabrata and Cryptococcus neoformans, which are yeast type fungi, and Aspergillus fumigatus, Arthroderma vanbreuseghemii, Arthroderma benhamiae, Microsporum canis, Trichophyton rubrum, and Rhizopus oryzae, which are filamentous fungi. Novel genes encoding virulence factors in C. albicans and C. glabrata have been identified by using the silkworm infection models. We here outline the benefits of using silkworm infection models and a strategy for identifying the genes responsible for pathogenicity of microorganisms such as fungi. © 2019 The Authors. Microbiology and Immunology Published by The Societies and John Wiley & Sons Australia, Ltd.
Topics: Animals; Bacteria; Bombyx; Candida; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Fungi; Mycoses; Virulence; Virulence Factors
PubMed: 30666711
DOI: 10.1111/1348-0421.12668 -
Current Medical Mycology Jun 2021The most common etiological agents of human dermatophytosis in various parts of the world are , , and . The main aim of this study was to design and evaluate a simple...
A simple multiplex polymerase chain reaction assay for rapid identification of the common pathogenic dermatophytes: Trichophyton interdigitale, Trichophyton rubrum, and Epidermophyton floccosum.
BACKGROUND AND PURPOSE
The most common etiological agents of human dermatophytosis in various parts of the world are , , and . The main aim of this study was to design and evaluate a simple and straightforward multiplex polymerase chain reaction (PCR) assay for reliable identification/differentiation of these species in clinical isolates.
MATERIALS AND METHODS
The reliable sequences of several molecular targets of dermatophytes species were used to design a multiplex PCR for the identification of common pathogenic dermatophytes. The isolates and clinical specimens examined in this study included seven standard strains of dermatophytes, 101 isolates of dermatophytes and non-dermatophyte molds/yeasts which had already been identified by sequencing or PCR-restriction fragment length polymorphism (RFLP), and 155 clinical samples from patients suspected of cutaneous mycoses.
RESULTS
Species-specific primer pairs for and / were designed based on the sequence data of the translation elongation factor 1-alpha gene, and the primers for targeted the specific sequence of the internal transcribed spacer region (ITS). The multiplex PCR successfully detected , /, and strains that were identified by sequencing or PCR-RFLP. However, the primer pairs selected for / cross-reacted with . In testing the PCR system directly for clinical samples, the proportion of positive multiplex PCR was higher than positive culture (68.1% vs. 55.4%, respectively).
CONCLUSION
The multiplex assay could detect three common agents out of several causal agents of dermatophytosis, namely , , and . Therefore, by adding pan-dermatophyte primers it can be used as a comprehensive detection/identification test.
PubMed: 35028478
DOI: 10.18502/cmm.7.2.7030