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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 -
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) Jul 2015Manifestations of infestations, such as tinea pedis, tinea cruris, and tinea corporis, are among the most common human skin diseases seen throughout the world. About... (Review)
Review
Manifestations of infestations, such as tinea pedis, tinea cruris, and tinea corporis, are among the most common human skin diseases seen throughout the world. About 80% of patients presenting with acute dermatophytosis respond well to topical antifungal treatment. However, the remaining 20% of patients progress into a chronic state of dermatophytosis, which is resistant to antifungal treatment. Therefore, it is necessary to have a better understanding and appreciation for the diverse immune responses to Trichophyton as this is critical for the development of therapeutic strategies for those individuals who suffer from a chronic manifestation of () infection. As a result, a comprehensive literature review was conducted to review and discuss previous studies that evaluated the human body's defense to infections and to understand why and how these fungal infections invade the host defense system. Our research revealed that a cell-mediated immune response is critical in defending the body against . However, this organism has mechanisms that enable it to evade the immune system. Therefore, a more successful treatment for chronic infection would involve targeting the mechanisms of that diminish the immune response, while restoring the cell-mediated immune response.
PubMed: 29376904
DOI: 10.3390/jof1020130 -
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 -
Journal of Fungi (Basel, Switzerland) Dec 2015Dermatophytes are keratinophilic fungi responsible for benign and common forms of infection worldwide. However, they can lead to rare and severe diseases in... (Review)
Review
Dermatophytes are keratinophilic fungi responsible for benign and common forms of infection worldwide. However, they can lead to rare and severe diseases in immunocompromised patients. Severe forms include extensive and/or invasive dermatophytosis, , deep dermatophytosis and Majocchi's granuloma. They are reported in immunocompromised hosts with primary (autosomal recessive CARD9 deficiency) or acquired (solid organ transplantation, autoimmune diseases requiring immunosuppressive treatments, HIV infection) immunodeficiencies. The clinical manifestations of the infection are not specific. Lymph node and organ involvement may also occur. Diagnosis requires both mycological and histological findings. There is no consensus on treatment. Systemic antifungal agents such as terbinafine and azoles (itraconazole or posaconazole) are effective. However, long-term outcome and treatment management depend on the site and extent of the infection and the nature of the underlying immunodeficiency.
PubMed: 29376922
DOI: 10.3390/jof2010004 -
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 -
Frontiers in Molecular Biosciences 2022The occurrence of chronic wounds is a major global health issue. These wounds are difficult to heal as a result of disordered healing mechanisms. The most common types... (Review)
Review
The occurrence of chronic wounds is a major global health issue. These wounds are difficult to heal as a result of disordered healing mechanisms. The most common types of chronic wounds are diabetic ulcers, pressure ulcers, arterial/venous ulcers and nonhealing surgical wounds. Although bacteria are an important cause of chronic nonhealing wounds, fungi also play a substantial role in them. The fungal infection rate varies with different chronic wound types, but overall, the prevalence of fungi is extremely underestimated in the clinical treatment and management of chronic wounds. Wounds and ulcers can be colonized by host cutaneous, commensal or environmental fungi and evolve into local infections, causing fungemia as well as invasive fungal disease. Furthermore, the fungi involved in nonhealing wound-related infections help commensal bacteria resist antibiotics and the host immune response, forcing wounds to become reservoirs for multiresistant species, which are considered a potential key factor in the microbial bioburden of wounds and ulcers. Fungi can be recalcitrant to the healing process. Biofilm establishment is the predominant mechanism of fungal resistance or tolerance to antimicrobials in chronic nonhealing wounds. yeast and filamentous fungi are the main fungi involved in chronic wound infection. Fungal species diversity and drug resistance phenotypes in different chronic nonhealing wound types will be emphasized. In this review, we outline the latest research on fungi in chronic wounds and discuss challenges and future perspectives related to diagnosing and managing chronic wounds.
PubMed: 36710878
DOI: 10.3389/fmolb.2022.1057766 -
Antibiotics (Basel, Switzerland) Oct 2022Fungal infections are one of the main causes of mortality and morbidity worldwide and taking into account the increasing incidence of strains resistant to classical...
Fungal infections are one of the main causes of mortality and morbidity worldwide and taking into account the increasing incidence of strains resistant to classical antifungal drugs, the development of new agents has become an urgent clinical need. Considering that thioxanthones are bioisosteres of xanthones with known anti-infective actions, their scaffolds were selected for this study. A small library of synthesized aminothioxanthones (-) was evaluated for in vitro antifungal activity against , , and ; for the active compounds, the spectrum was further extended to other clinically relevant pathogenic fungi. The results showed that only compounds , , and exhibited inhibitory and broad-spectrum antifungal effects. Given the greater antifungal potential presented, compound was the subject of further investigations to study its anti-virulence activity and in an attempt to elucidate its mechanism of action; compound seems to act predominantly on the cellular membrane of ATCC 10231, altering its structural integrity, without binding to ergosterol, while inhibiting two important virulence factors-dimorphic transition and biofilm formation-frequently associated with pathogenicity and resistance. In conclusion, the present work proved the usefulness of thioxanthones in antifungal therapy as new models for antifungal agents.
PubMed: 36358143
DOI: 10.3390/antibiotics11111488 -
Frontiers in Microbiology 2022is the most common causative agent of dermatophytosis worldwide and uses keratinized substrates such as skin and nails as its main source of nutrition during infection....
is the most common causative agent of dermatophytosis worldwide and uses keratinized substrates such as skin and nails as its main source of nutrition during infection. Its pathogenic character relies on colonization and viability maintenance at the target host sites. Since fungal physiology must adapt and respond to host conditions for the successful establishment of infection, biological mechanisms are constantly being triggered by to guarantee its survival in the host environment. The ability of this fungus to sense and modulate the secretion of specific proteases according to environmental pH signaling is considered as a pivotal virulence factor for effective invasion and persistence of infection in the host. Transcriptional regulation of genes encoding specific proteases, such as peptidases, is a key biological process that drives physiological modulation to meet fungal requirements. It accomplishes a robust balance among transcript isoforms that can be directed to perform distinct cellular functions. Thus, alternative splicing mechanisms are suitable for fungal cells to establish a balance toward reprogramming protein translation to impair or boost physiological conditions. In this study, we investigated the role of alternative splicing, especially intron retention events, in generating isoforms of virulence factors in mediated by transcriptional coordination of the protein StuA, a recently described transcription factor in this fungus. By analyzing the previous gene expression data provided by RNA-sequencing and after validation by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), we observed that two peptidase-coding genes (TERG_00734 and TERG_04614) could be direct targets of alternative splicing in the presence of keratin. Furthermore, protease isoforms generated by alternative splicing in were also detected in a co-culture with human keratinocytes, highlighting the role of these proteins in keratin deconstruction. Our results strongly suggest the influence of StuA on the regulation of virulence factors in and dermatophyte infections by triggering the transcription of the peptidase genes mentioned above in an alternative splicing-independent balance. The results elucidate how fungal cells drive alternate splicing to promote physiological adaptations and show that transcriptional regulation and virulence traits are robust elements required for dermatophyte infection.
PubMed: 35783403
DOI: 10.3389/fmicb.2022.930398 -
Microbial Biotechnology Feb 2022Trichophyton rubrum is responsible for the majority of dermatophytosis. Current systemic and topical antifungals against dermatophytosis are often tedious and sometimes...
Trichophyton rubrum is responsible for the majority of dermatophytosis. Current systemic and topical antifungals against dermatophytosis are often tedious and sometimes unsatisfactory. Antimicrobial photodynamic therapy (aPDT) is a non-invasive alternative suitable for the treatment of superficial fungal infections. This work investigated the photodynamic inactivation efficacy and effects of aloe-emodin (AE), a natural photosensitizer (PS) against T. rubrum microconidia in vitro, and evaluated the treatment effects of AE-mediated aPDT for T. rubrum-caused tinea corporis in vivo and tinea unguium ex vivo. The photodynamic antimicrobial efficacy of AE on T. rubrum microconidia was evaluated by MTT assay. The inhibition effect of AE-mediated aPDT on growth of T. rubrum was studied. Intracellular location of AE, damage induced by AE-mediated aPDT on cellular structure and surface of microconidia and generation of intracellular ROS were investigated by microscopy and flow cytometry. The therapeutic effects of AE-mediated aPDT against dermatophytosis were assessed in T. rubrum-caused tinea corporis guinea pig model and tinea unguium ex vivo model. AE-mediated aPDT effectively inactivated T. rubrum microconidia in a light energy dose-dependent manner and exhibited strong inhibitory effect on growth of T. rubrum. Microscope images indicated that AE is mainly targeted to the organelles and caused damage to the cytoplasm of microconidia after irradiation through generation of abundant intracellular ROS. AE-mediated aPDT demonstrated effective therapeutic effects for T. rubrum-caused tinea corporis on guinea pig model and tinea unguium in ex vivo model. The results obtained suggest that AE is a potential PS for the photodynamic treatment of dermatophytosis caused by T. rubrum, but its permeability in skin and nails needs to be improved.
Topics: Aloe; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Arthrodermataceae; Emodin; Guinea Pigs; Onychomycosis; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Tinea; Trichophyton
PubMed: 34165875
DOI: 10.1111/1751-7915.13875