Triterpenoids and Their Glycosides from Glinus Oppositifolius with Antifungal Activities against Microsporum Gypseum and Trichophyton Rubrum.
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ABSTRACT:
SUBMITTER: Zhang D
PROVIDER: S-EPMC6631934 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Keratin is important and needed for the growth of dermatophytes in the host tissue. In turn, the ability to invade keratinised tissues is defined as a pivotal virulence attribute of this group of medically important fungi. The host-dermatophyte interaction is accompanied by an adaptation of fungal metabolism that allows them to adhere to the host tissue as well as utilize the available nutrients necessary for their survival and growth. Dermatophyte infections pose a significant epidemiological and clinical problem. Trichophyton rubrum is the most common anthropophilic dermatophyte worldwide and its typical infection areas include skin of hands or feet and nail plate. In turn, Microsporum canis is a zoophilic pathogen, and mostly well known for ringworm in pets, it is also known to infect humans. The aim of the study was to compare the intracellular metabolite content in the T. rubrum and M. canis during keratin degradation using liquid chromatography system coupled with tandem mass spectrometer (LC-MS/MS). The metabolite "fingerprints" revealed compounds associated with amino acids metabolism, carbohydrate metabolism related to the glycolysis and the tricarboxylic acid cycle (TCA), as well as nucleotide and energy metabolism. The metabolites such as kynurenic acid, L-alanine and cysteine in case of T. rubrum as well as cysteine and riboflavin in case of M. canis were detected only during keratin degradation what may suggest that these compounds may play a key role in the interactions of T. rubrum and M. canis with the host tissue. The metabolomic results were completed by qPCR gene expression assay. Our findings suggest that metabolomic analysis of T. rubrum and M. canis growing in culture media that mimic the dermatophyte infection could allow the understanding of processes involved in the pathogenesis of dermatophytes.
| S-EPMC7889620 | biostudies-literature
Project description:Superficial mycoses caused by dermatophyte fungi are among the most common infections worldwide, yet treatment is restricted by limited effective drugs available, drug toxicity, and emergence of drug resistance. The stilbene fluorescent brightener calcofluor white (CFW) inhibits fungi by binding chitin in the cell wall, disrupting cell wall integrity, and thus entails a different mechanism of inhibition than currently available antifungal drugs. To identify novel therapeutic options for the treatment of skin infections, we compared the sensitivity of representative strains of the dermatophyte Trichophyton rubrum and Candida albicans to CFW and a panel of fluorescent brighteners and phytoalexin compounds. We identified the structurally related stilbene fluorescent brighteners 71, 85, 113 and 134 as fungicidal to both T. rubrum and C. albicans to a similar degree as CFW, and the stilbene phytoalexins pinosylvan monomethyl ether and pterostilbene inhibited to a lesser degree, allowing us to develop a structure-activity relationship for fungal inhibition. Given the abilities of CFW to absorb UV(365 nm) and bind specifically to fungal cell walls, we tested whether CFW combined with UV(365 nm) irradiation would be synergistic to fungi and provide a novel photodynamic treatment option. However, while both treatments individually were cytocidal, UV(365 nm) irradiation reduced sensitivity to CFW, which we attribute to CFW photoinactivation. We also tested combination treatments of CFW with other fungal inhibitors and identified synergistic interactions between CFW and some ergosterol biosynthesis inhibitors in C. albicans. Therefore, our studies identify novel fungal inhibitors and drug interactions, offering promise for combination topical treatment regimes for superficial mycoses.
| S-EPMC3391284 | biostudies-literature
Project description:In vitro susceptibility testing for Trichophyton rubrum has shown resistance to terbinafine, azoles and amorolfine, locally, but epidemiological cutoffs are not available. In order to assess the appropriateness of current first-line antifungal treatment for T. rubrum in China, we characterized antifungal susceptibility patterns of Chinese T. rubrum strains to nine antifungals and also described the upper limits of wild-type (WT) minimal inhibitory concentrations (MIC) (UL-WT) based on our study and another six studies published during the last decades. Sixty-two clinical isolates originating from seven provinces in China were identified as T. rubrum sensu stricto; all Chinese strains showed low MICs to eight out of nine antifungal drugs. Terbinafine (TBF) showed the lowest MICs of all antifungal classes tested in both the Chinese and global groups, with a 97.5% UL-WT MIC-value of 0.03 mg/L. No non-WT isolates were observed for TBF in China, but were reported in 18.5% of the global group. Our study indicated that TBF was still the most active drug for Chinese T. rubrum isolates, and all strains were within the WT-population. TBF therefore remains recommended for primary therapy to dermatophytosis caused by T. rubrum in China now, but regular surveillance of dermatophytes and antifungal susceptibility is recommended.
| S-EPMC7946697 | biostudies-literature
Project description:Trichoderma rubrum (T. rubrum) is one of the important pathogens because it is the cause of most dermatomycosis. The treatment of Trichophyton rubrum infection is time-consuming and very expensive; it is easy for the infections to reoccur, leading to therapeutic failures, persistence, and chronic infection. These issues have inspired researchers to study natural alternative therapies instead. Cnidium monnieri (L.), as a kind of traditional Chinese medicine, has a variety of pharmacological activities and a wide range of applications, so it has a high potential for researching and economic value. We detected the effect of aqueous extract of C. monnieri (L.) on the activity of T. rubrum by Cell Count Kit-8 assay (CCK-8), and we found that 128 and 256 μg/ml of aqueous extracts of C. monnieri (L.) co-cultured with T. rubrum for 24 h showed the inhibitory effect on T. rubrum. The results of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed that aqueous extract of C. monnieri (L.) damaged the T. rubrum. At the same time, mass spectrometry screening with T. rubrum before and after the treatment of 256 μg/ml of aqueous extracts of C. monnieri (L.) showed that 966 differentially expressed proteins were detected, including 524 upregulated differentially expressed genes (DEGs) and 442 downregulated DEGs. The most significantly downregulated protein was chitin synthase (CHS); and the results of qRT-PCR and Western blotting demonstrated that the expression level of CHS was downregulated in the 256 μg/ml group compared with the control group. The study showed that the aqueous extract of C. monnieri (L.) could destroy the morphology of mycelia and the internal structure of T. rubrum, and it could inhibit the growth of T. rubrum. The antifungal effect of aqueous extract of C. monnieri (L.) may be related to the downregulation of the expression of CHS in T. rubrum, and CHS may be one of the potential targets of its antifungal mechanism. We concluded that aqueous extract from C. monnieri (L.) may be a potential candidate for antifungal agents.
| S-EPMC8417377 | biostudies-literature
Project description:IntroductionDermatophytosis is a superficial fungal infection limited to the stratum corneum of the epidermis, or to the hair and nails, and constitutes an important public health problem because of its high prevalence and associated morbidity. Dermatophyte fungi, especially 2 species, Trichophyton rubrum and Trichophyton mentagrophytes, are the predominant pathogens. Topical antifungal drugs, mainly azoles or allyamines, are currently used for the treatment of dermatophytoses, although in some cases, such as in nail and hair involvement, systemic treatment is required. However, therapeutic efficacy of current antifungal agents can be limited by their side effects, costs, and the emergence of drug resistance among fungi. Plant extracts represent a potential source of active antimicrobial agents, due to the presence of a variety of chemical bioactive compounds. In the present work, we evaluated in silico and in vitro the antifungal activity of an extract of the medicinal plant Cardiospermum halicacabum against T. rubrum suggesting a potential interaction with Hsp90 as playing an important role in both pathogenicity and drug susceptibility of T. rubrum.MethodsWe investigated in vitro the effect of different concentrations of C. halicacabum (from 500 to 31.25 µg) against a clinical isolate of T. rubrum. Furthermore, using a computational assessment, the interaction between different C. halicacabum active compounds and the fungal Hsp90 was also investigated.ResultsOur results indicate a clear-cut antifungal activity of the total plant extract at the highest concentrations (500 and 250 µg). Among all tested C. halicacabum compounds, the luteolin and rutin molecules have been identified in silico as the most important potential inhibitors of Hsp90. Based on these data, luteolin and rutin were also individually assessed for their antifungal activity. Results demonstrate that both substances display an antifungal effect, even if lower than that of the total plant extract.ConclusionOur data indicate a strong fungistatic effect of C. halicacabum against T. rubrum, suggesting its potential therapeutic efficacy in the treatment of dermatophytoses. Additionally, C. halicacabum compounds, and particularly luteolin and rutin, are all possible Hsp90 interactors, explaining their fungistatic activity.
| S-EPMC6047602 | biostudies-literature
Project description:The diseases caused by dermatophytes are common among several other infections which cause serious threat to human health. It is evident that enzyme squalene epoxidase is responsible for prolonged dermatophyte infection and it is appealing to note that this enzyme is also responsible for fatty acid synthesis in these groups of fungi. In the present study, terbinafine drug which targets enzyme squalene epoxidase has been explored to design its various novel analogues. The present study suggests that many more prominent drug analogues could be constituted which may be crucial towards designing new drug candidates. In the present study, we have designed a series of such analogues viz. [(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)(naphthalen-1-ylmethyl)amine, N-[8-({[(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)amino}methyl)naphthalen-1-yl]-2-(sulfoamino) acetamide, {[4-(dihydroxyamino)-8-({[(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)amino}methyl)naphthalen-1-yl]sulfanyl}methanol and (R)-{[4-({[(2E,6R)-6,7-dimethyloct-2-en-4-yn-1-yl](methyl)amino}methyl)-5-[(hydroxysulfamoyl)amino]naphthalen-1-yl]amino}sulfinic acid. Moreover, further by molecular docking approach the binding between enzyme and designed analogues was further analysed. The present preliminary report suggested a considerably good docking interaction score of -338.75 kcal/mol between terbinafine and squalene epoxidase from Trichophyton rubrum. This preliminary study implies that few designed candidate ligands can be effectual towards the activity of this enzyme and can play crucial role in pathogenesis control of T. rubrum.
| S-EPMC4456508 | biostudies-literature
Project description: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 Pseudomonas aeruginosa SS14 on planktonic cells of Trichophyton rubrum and Trichophyton mentagrophytes, 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 T. rubrum and T. mentagrophytes 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.
| S-EPMC7451867 | biostudies-literature
Project description:Conidia are considered to be the primary cause of skin and nail infections by Trichophyton rubrum. A cDNA microarray containing 10112 ESTs was developed and used to estimate the relative gene expression levels and changes of gene expression during conidial germination in time-course experiments. Keywords: time course
2007-03-27 | GSE5083 | GEO
Project description:Dermatophytes are challenging to treat because they have developed many strategies to neutralize the stress triggered by antifungals. Drug tolerance is achieved by mechanisms such as drug efflux and biofilm formation, and cellular efflux is a consequence of the synergistic and compensatory regulation of efflux pumps. Alternative splicing (AS) has also been considered as a mechanism that enhances fungal adaptive responses. We used RNA-seq data from the dermatophyte Trichophyton rubrum exposed to undecanoic acid (UDA) to search for and validate AS in genes encoding efflux pumps. The magnitude of this phenomenon was evaluated using UDA and other antifungals (caspofungin, itraconazole, and terbinafine) in planktonic and biofilm cultures. In addition to the conventional isoforms, the efflux pump encoded by TERG_04309 presented two intron-retained isoforms. Biofilms trigger the simultaneous production of at least two isoforms. The intron-retained isoforms showed short lengths and topologically different organization. Furthermore, we identified the putative interaction of efflux pumps (TERG_04309 and TERG_04224). Co-expression of these genes suggests a synergistic action in antifungal resistance. Our data provide new insights into drug tolerance related to differential isoform usage and the co-expression of stress-responsive genes, which may lead to higher antifungal resistance, mainly in biofilms.
| S-EPMC9410333 | biostudies-literature
Project description:Around 90% of chronic dermatophyte infections are caused by the fungi Trichophyton mentagrophytes and Trichophyton rubrum. One of the causes of the chronic infection resides in the immunosuppressive effects of the cell-wall components of these organisms. Therefore we have attempted to identify the chemical structure of galactomannan, one of the major cell-wall components. The cell-wall polysaccharides secreted by T. mentagrophytes and T. rubrum were isolated from the culture medium and fractionated into three subfractions by DEAE-Sephadex chromatography. Analysis of each subfraction by NMR indicated that there are two kinds of polysaccharides present, i.e. mannan and galactomannan. The mannan has a linear backbone consisting of alpha1,6-linked mannose units, with alpha1,2-linked mannose units as side chains. The core mannan moiety of the galactomannan was analysed by a sequential NMR assignment method after removing the galactofuranose units by acid treatment. The result indicates that the mannan moiety has a linear repeating structure of alpha1,2-linked mannotetraose units connected by an alpha1,6 linkage. The H-1 signals of the two intermediary alpha1, 2-linked mannoses of the tetraose unit showed a significant upfield shift (Deltadelta=0.05-0.08 p.p.m.), due to the steric effect of an alpha1,6-linked mannose unit. The attachment point of the galactofuranose units was determined at C-3 of the core mannan by the assignment of the downfield-shifted 13C signals of the galactomannan compared with those of the acid-modified product. In these galactomannans there were no polygalactofuranosyl chains which have been found in Penicillium charlesii and Aspergillus fumigatus.
| S-EPMC1218309 | biostudies-other