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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 -
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 -
Evidence-based Complementary and... 2020, among other dermatophytes, is a major causative agent for superficial dermatomycoses like onychomycosis and tinea pedis, especially among pediatric and geriatric...
BACKGROUND
, among other dermatophytes, is a major causative agent for superficial dermatomycoses like onychomycosis and tinea pedis, especially among pediatric and geriatric populations. Ellagic acid (EA) and shikonin (SK) have been reported to have many bioactivities, including antifungal activity. However, the mechanism of EA and SK on has not yet been reported.
OBJECTIVES
The purposes of this study were to evaluate the antifungal activities of EA and SK against and to illuminate the underlying action mechanisms.
METHODS
The effect of EA (64, 128, and 256 g/mL) and SK (8, 4, and 2 g/mL) on was investigated with different doses via detecting cell viability, ultrastructure with using a scanning electron microscope (SEM), cell apoptosis and necrosis by using the flow cytometry instrument technique (FCIT), and the ergosterol biosynthesis pathway-related fungal cell membrane key gene expressions in vitro.
RESULTS
SEM detection revealed that the cell surface was shrivelled, folded, and showed deformation and expansion, visible surface peeling, and broken hyphae, and cell contents overflowed after being treated with EA and SK; the cell apoptosis rate was significantly increased in dose-dependent manner after was treated with EA and SK; the qPCR results showed that mRNA expression of MEP4 and SUB1 was downregulated in EA- and SK-treated groups.
CONCLUSIONS
Overall, our results revealed the underlying antifungal mechanism of EA and SK, which may be related to the destruction of the fungal cell membrane and inhibition of C14 demethylase and the catalytic rate of squalene cyclooxidase in the ergosterol biosynthesis pathway via downregulation of MEP4 and SUB1, suggesting that EA and SK have the potential to be developed further as a natural antifungal agent for clinical use.
PubMed: 33193798
DOI: 10.1155/2020/7305818 -
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 -
PloS One 2015Antimicrobial photodynamic inhibition (aPI) utilizes radical stress generated from the excitation of a photosensitizer (PS) with light to destroy pathogens. Its use...
Antimicrobial photodynamic inhibition (aPI) utilizes radical stress generated from the excitation of a photosensitizer (PS) with light to destroy pathogens. Its use against Trichophyton rubrum, a dermatophytic fungus with increasing incidence and resistance, has not been well characterized. Our aim was to evaluate the mechanism of action of aPI against T. rubrum using curcumin as the PS in both free and nanoparticle (curc-np) form. Nanocarriers stabilize curcumin and allow for enhanced solubility and PS delivery. Curcumin aPI, at optimal conditions of 10 μg/mL of PS with 10 J/cm² of blue light (417 ± 5 nm), completely inhibited fungal growth (p<0.0001) via induction of reactive oxygen (ROS) and nitrogen species (RNS), which was associated with fungal death by apoptosis. Interestingly, only scavengers of RNS impeded aPI efficacy, suggesting that curcumin acts potently via a nitrosative pathway. The curc-np induced greater NO˙ expression and enhanced apoptosis of fungal cells, highlighting curc-np aPI as a potential treatment for T. rubrum skin infections.
Topics: Antifungal Agents; Capsules; Cell Line; Curcumin; Free Radical Scavengers; Humans; Kinetics; Light; Microbial Sensitivity Tests; Nanoparticles; Phagocytosis; Photosensitizing Agents; Reactive Nitrogen Species; Reactive Oxygen Species; Stress, Physiological; Trichophyton
PubMed: 25803281
DOI: 10.1371/journal.pone.0120179 -
Frontiers in Genetics 2022Lysine crotonylation is a newly discovered post-translational modification (PTM) with key roles in various important regulatory pathways. Despite its functional...
Lysine crotonylation is a newly discovered post-translational modification (PTM) with key roles in various important regulatory pathways. Despite its functional significance, there is limited knowledge about crotonylation in fungi. is the most common fungal pathogen in human infection and is considered a model organism of dermatophytes and human pathogenic filamentous fungi. In this study, we obtained a proteome-wide crotonylation profile of , leading to the identification of 14,019 crotonylated sites on 3144 proteins. The crotonylated proteins were significantly involved in translation and in various metabolic and biosynthetic processes. Some proteins related to fungal pathogenicity were also found to be targets of crotonylation. In addition, extensive crotonylation was found on histones, suggesting a role in epigenetic regulation. Furthermore, about half of the crotonylated proteins were specific to either the conidial or the mycelial stage, and functional enrichment analysis showed some differences between the two stages. The results suggest that the difference in crotonylation between the two stages is not due to differences in protein abundance. Crosstalk of crotonylation with acetylation, propionylation, and succinylation suggests distinct regulatory roles. This study is the first crotonylation analysis in dermatophytes and human pathogenic filamentous fungi. These results represent a solid foundation for further research on PTM regulatory mechanisms in fungi and should facilitate improved antifungal strategies against these medical important species.
PubMed: 35356433
DOI: 10.3389/fgene.2022.832668 -
Archives of Razi Institute Dec 2022Using microorganisms to make this nanomaterial is a new research technique. In a culture medium, was permitted to biosynthesis silver nanoparticles. This study used , a...
Using microorganisms to make this nanomaterial is a new research technique. In a culture medium, was permitted to biosynthesis silver nanoparticles. This study used , a dermatophytes fungus, to make silver nanoparticles. These species' clinical strains were produced in a medium containing mineral salt and cultured for 5-7 days at 25°C. Each culture's cell-free filtrate was taken and used to make AgNps in the presence of 1 mM AgNO3. The reduction of Ag+ ions in metal nanoparticles was virtually studied by observing the colour of the solution, which changed to a reddish-light brown after 72 hours. SEM was used to establish the presence of AgNo3. The presence of AgNPs was confirmed by SEM, which revealed that they are primarily spherical and 100nm in size. Furthermore, the findings showed that silver nanoparticles have antifungal activity against both infections in a concentration-dependent manner. At (150 ppm) of AgNPs, the growth decreased.
Topics: Animals; Arthrodermataceae; Antifungal Agents; Metal Nanoparticles; Silver
PubMed: 37274919
DOI: 10.22092/ARI.2022.358495.2235 -
Frontiers in Microbiology 2020The ability of fungi to sense environmental stressors and appropriately respond is linked to secretory system functions. The dermatophyte infection process depends on an...
The ability of fungi to sense environmental stressors and appropriately respond is linked to secretory system functions. The dermatophyte infection process depends on an orchestrated signaling regulation that triggers the transcription of genes responsible for adherence and penetration of the pathogen into host-tissue. A high secretion system is activated to support the host-pathogen interaction and assures maintenance of the dermatophyte infection. The gateway of secretion machinery is the endoplasmic reticulum (ER), which is the primary site for protein folding and transport. Current studies have shown that ER stress that affects adaptive responses is primarily regulated by UPR and supports fungal pathogenicity; this has been assessed for yeasts and , in regard to how these fungi cope with host environmental stressors. Fungal UPR consists of a transmembrane kinase sensor (Ire1/IreA) and a downstream target Hac1/HacA. The active form of Hac is achieved via non-spliceosomal intron removal promoted by endonuclease activity of Ire1/IreA. Here, we assessed features of HacA and its involvement in virulence and susceptibility in . Our results showed that exposure to antifungals and ER-stressing agents initiated the activation of HacA from . Interestingly, the activation occurs when a 20 nt fragment is removed from part of the exon-2 and part of intron-2, which in turn promotes the arisen of the DNA binding site motif and a dimer interface domain. Further, we found changes in the cell wall and cellular membrane composition in the Δ mutant as well as an increase in susceptibility toward azole and cell wall disturbing agents. Moreover, the Δ mutant presented significant defects in important virulence traits like thermotolerance and growth on keratin substrates. For instance, the development of the Δ mutant was impaired in co-culture with keratinocytes or human nail fragments. Changes in the pro-inflammatory cytokine release were verified for the Δ mutant during the co-culture assay, which might be related to differences in pathogen-associated molecular patterns (PAMPs) in the cell wall. Together, these results suggested that HacA is an integral part of physiology and virulence, implying that it is an important molecular target for antidermatophytic therapy.
PubMed: 32153523
DOI: 10.3389/fmicb.2020.00193 -
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 -
PloS One 2019Trichophyton rubrum is a human pathogenic fungus. As a dermatophyte it causes athlete's foot, fungal infection of nails, jock itch and ringworm. The pigmentation of T....
Trichophyton rubrum is a human pathogenic fungus. As a dermatophyte it causes athlete's foot, fungal infection of nails, jock itch and ringworm. The pigmentation of T. rubrum is variable and can range from white or yellow to wine-red. We demonstrate that the pigmentation is strongly influenced by pH. Under alkaline conditions, T. rubrum has a red pigmentation, whereas at acid conditions, T. rubrum has a yellow pigmentation. Moreover, the color change immediately from yellow to red by adding NaOH and reverse immediately from red to yellow by adding HCl. We suggest that the chemical compound Xanthomegnin is responsible for red as well for yellow pigmentation in T. rubrum. To figure out, why T. rubrum has red pigmentation on Trichophyton medium, adjust to alkaline, but not on Synthetic-Complete medium, also adjusted to alkaline, we measure the pH of liquid media, adjusted to pH 3.5, 6 and 8, over a period of four weeks. The pH of both cultivation media changes significantly, with a maximum of five pH levels. Whereas the Trichophyton medium, initially adjusted to pH 8, stays alkaline, the pH of the Synthetic-Complete medium drops to acid conditions. The acidification of the SC medium and the alkalization of the Trichophyton medium explains the different pigment color of the T. rubrum colonies.
Topics: Culture Media; Humans; Hydrogen-Ion Concentration; Naphthoquinones; Pigmentation; Pigments, Biological; Trichophyton
PubMed: 31504066
DOI: 10.1371/journal.pone.0222333