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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 -
Frontiers in Fungal Biology 2022The growth and development of organisms depend on nutrient availability. Dermatophytes must sense nutrient levels and adapt to the host environment to colonize human and...
The growth and development of organisms depend on nutrient availability. Dermatophytes must sense nutrient levels and adapt to the host environment to colonize human and animal keratinized tissues. Owing to the clinical importance of the genus, this study compared the expression profile of genes involved in metabolism, cell cycle control, and proteases in two species, , and , in response to nutrients and environmental pH. In addition, we evaluated the activity of enzymes in the tricarboxylic acid, glyoxylate, and methylcitrate cycles. Moreover, the effects of interruption of the transcription factor on in the same conditions as for the wild-type strain were determined. Our analyses revealed specific responses in each species to the nutritional and pH variation. An improved adaptation of to keratin was observed, compared with that of . growth in buffered keratin media indicated pH 8.0 as an optimal pH condition for metabolic activity, which differed from that for . Tricarboxylic acid components in showed increased enzymatic activity and transcript accumulation. In , a higher activity of enzymes in glyoxylate and methylcitrate cycles was observed, with no direct correlation to the transcriptional profile. fungal metabolism suggests the requirement of anaplerotic pathways in the late cultivation period. The identified differences between and may represent determinants for adaptation to the host and the incidence of infection with each species.
PubMed: 37746184
DOI: 10.3389/ffunb.2022.858968 -
Journal of Clinical Microbiology Dec 2023Dermatophyte infections (a.k.a. ringworm, tinea) affect an estimated 20%-25% of the world's population. In North America, most dermatophytoses are caused by or species...
Dermatophyte infections (a.k.a. ringworm, tinea) affect an estimated 20%-25% of the world's population. In North America, most dermatophytoses are caused by or species complexes. Severe and antifungal-resistant dermatophytoses are a growing global public health problem. A new species of the species complex, , has recently emerged and is notable for the severe infections it causes, its propensity for antifungal resistance, and its global spread. In this issue of the , C. F. Cañete-Gibas, J. Mele, H. P. Patterson, et al. (J Clin Microbiol 61:e00562-23, 2023, https://doi.org/10.1128/JCM.00562-23) summarize the results of speciation and AFST performed on North American dermatophyte isolates received at a fungal diagnostic reference laboratory. Within their collection, 18.6% of isolates were resistant to terbinafine (a first-line oral antifungal for dermatophytoses), and similar proportions of and demonstrated terbinafine resistance. The authors also found that has been present in North America since at least 2017. These findings highlight the importance of increased surveillance efforts to monitor trends in severe and antifungal-resistant dermatophytoses and the need for antifungal stewardship efforts, the success of which is contingent upon improving laboratory capacity for dermatophyte speciation and AFST.
Topics: Humans; Terbinafine; Antifungal Agents; Arthrodermataceae; Tinea; Microbial Sensitivity Tests; Trichophyton; Drug Resistance, Fungal
PubMed: 38014979
DOI: 10.1128/jcm.00903-23 -
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 -
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 -
Pharmaceutics Mar 2022Fungal diseases affect more than 1 billion people worldwide. The constant global changes, the advent of new pandemics, and chronic diseases favor the diffusion of fungal...
Fungal diseases affect more than 1 billion people worldwide. The constant global changes, the advent of new pandemics, and chronic diseases favor the diffusion of fungal pathogens such as , , , , and . In this work, a series of nitrofuran derivatives were synthesized and tested against different fungal species; most of them showed inhibitory activity, fungicide, and fungistatic profile. The minimal inhibitory concentration (MIC) values for the most potent compounds range from 0.48 µg/mL against (compound ) and (compounds and ) to 0.98 µg/mL against and (compounds , , , and , , , respectively), and 3.9 µg/mL against and strains (compounds and , respectively). In addition, all compounds showed low toxicity when tested in vitro on lung cell lines (A549 and MRC-5) and in vivo in larvae. Many of them showed high selectivity index values. Thus, these studied nitrofuran derivatives proved to be potent against different fungal species, characterized by low toxicity and high selectivity; for these reasons, they may become promising compounds for the treatment of mycoses.
PubMed: 35335969
DOI: 10.3390/pharmaceutics14030593 -
Journal of Applied Microbiology Aug 2022This work examines the available scientific evidence about the efficiency of essential oils (EO) as an alternative therapy to traditional treatment of fungal infections,... (Meta-Analysis)
Meta-Analysis Review
AIMS
This work examines the available scientific evidence about the efficiency of essential oils (EO) as an alternative therapy to traditional treatment of fungal infections, including onychomycosis, assessing the effect of the three EO most frequently studied for their antifungal activity (thyme, cinnamon and tea tree EO) against three causative agents of fungal diseases in humans: Trichophyton rubrum, Trichophyton mentagrophytes complex and Candida albicans.
METHODS AND RESULTS
The PRISMA statement protocol was followed to conduct a bibliographical search and 54 articles that met all the inclusion criteria were retrieved. Differences were observed in the MIC and MFC values depending on the micro-organism strain and the EO used. The lowest MIC were observed with Cinnamomum zeylanicum EO (0.013-1120 μl ml ) against the three micro-organisms. For MFC, the lowest value was found for Thymus vulgaris EO (4.2 μl ml ) against Trichophyton rubrum.
CONCLUSIONS
The antifungal effects of EO could be a very promising solution to overcome the therapeutic shortcomings of antimycotic medication. More experiments are needed to examine the properties of these oils to devise effective and nonaggressive therapies for treatment of dermatophytosis.
SIGNIFICANCE AND IMPACT OF STUDY
The results indicate that EO remain good candidates for future treatments and could provide a solution for failed medications and/or adverse reactions to current pharmacological treatments.
Topics: Antifungal Agents; Arthrodermataceae; Cinnamomum zeylanicum; Complementary Therapies; Humans; Microbial Sensitivity Tests; Oils, Volatile; Tinea
PubMed: 35332625
DOI: 10.1111/jam.15539 -
Journal of Fungi (Basel, Switzerland) Jan 2022Terbinafine resistance in species has emerged and appears to be increasing. A new EUCAST susceptibility testing method and tentative ECOFFs were recently proposed for ....
Terbinafine resistance in species has emerged and appears to be increasing. A new EUCAST susceptibility testing method and tentative ECOFFs were recently proposed for . Terbinafine resistance and target gene mutations were detected in 16 Danish isolates in 2013-2018. In this study, samples/isolates submitted for dermatophyte susceptibility testing 2019-2020 were examined. Species identification (ITS sequencing for species complex (SC) isolates), EUCAST MICs and squalene epoxidase (SQLE) profiles were obtained. Sixty-three isolates from 59 patients were included. accounted for 81% and SC for 19%. Approximately 60% of and SC isolates were terbinafine non-wildtype and/or had known/novel SQLE mutations with possible implications for terbinafine MICs. All infections with terbinafine-resistant SC isolates were caused by . Compared to 2013-2018, the number of patients with terbinafine-resistant isolates increased. For , this is partly explained by an increase in number of requests for susceptibility testing. Terbinafine-resistant was first detected in 2018, but accounted for 19% of resistance (4 of 21 patients) in 2020. In conclusion, terbinafine resistance is an emerging problem in Denmark. Population based studies are warranted and susceptibility testing is highly relevant in non-responding cases.
PubMed: 35205904
DOI: 10.3390/jof8020150 -
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 -
Biotechnology Reports (Amsterdam,... Sep 2020Dermatophytes are responsible for a majority of fungal infections in humans and other vertebrates, causing dermatophytosis. Treatment failures are often associated with...
Dermatophytes are responsible for a majority of fungal infections in humans and other vertebrates, causing dermatophytosis. Treatment failures are often associated with biofilm formation, making dermatophytes resistant to antifungals. In this study, effects of a rhamnolipid (RL-SS14) produced by SS14 on planktonic cells of and , their biofilm formation, and disruption of mature biofilms were assessed. The composition of RL-SS14 was analysed using FTIR, HPLC-ESI-MS, and GC-MS. Minimum inhibitory concentrations against the planktonic forms of and were 0.5 mg/mL and 0.125 mg/mL, respectively. Crystal-violet (biofilm biomass) and safranin (extracellular matrix) staining revealed that RL-SS14 significantly inhibited biofilm formation and also reduced preformed biofilms in a dose-dependent manner. Microscopic visualization of treated biofilms via SEM, AFM, and CLSM revealed marked morphological damage, cell death, and reduced extracellular matrix. The results indicate the potential of RL-SS14 as an anti-biofilm agent against dermatophytes.
PubMed: 32884912
DOI: 10.1016/j.btre.2020.e00516