Dermatophyte Trichophyton Rubrum Research Articles

Design of Two Alternative Routes for the Synthesis of Naftifine and Analogues as Potential Antifungal Agents.

Two practical and efficient approaches have been implemented as alternative procedures for the synthesis of naftifine and novel diversely substituted analogues 16 and 20 in good to excellent yields, mediated by Mannich-type reactions as the key step of the processes. In these approaches, the γ-aminoalcohols 15 and 19 were obtained as the key intermediates and their subsequent dehydration catalyzed either by Brønsted acids like H2SO4 and HCl or Lewis acid like AlCl3, respectively, led to naftifine, along with the target allylamines 16 and 20. The antifungal assay results showed that intermediates 18 (bearing both a β-aminoketo- and N-methyl functionalities in their structures) and products 20 were the most active. Particularly, structures 18b, 18c, and the allylamine 20c showed the lowest MIC values, in the 0.5–7.8 µg/mL range, against the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Interesting enough, compound 18b bearing a 4-Br as the substituent of the phenyl ring, also displayed high activity against Candida albicans and Cryptococcus neoformans with MIC80 = 7.8 µg/mL, being fungicide rather than fungistatic with a relevant MFC value = 15.6 µg/mL against C. neoformans.

Blad-containing oligomer: a novel fungicide used in crop protection as an alternative treatment for tinea pedis and tinea versicolor.

The lack of novel antifungal drugs and the increasing incidence and severity of fungal infections are major concerns worldwide. Herein, we tested the activity of the Blad-containing oligomer (BCO), a new antifungal molecule already in use for agriculture, on Malassezia spp. and dermatophytes, the causal agents of human tinea versicolor and tinea pedis. Given the lack of a standard method for Malassezia susceptibility testing and the plethora of published methods, we also developed an improved method for this genus. The efficacy of BCO was assessed in vitro and compared to that of the drugs currently utilized in the treatment of tinea versicolor (fluconazole and itraconazole) and tinea pedis (itraconazole and terbinafine). For dermatophytes, the standard microdilution broth-based method was used, with small adjustments, and several broth formulations and inocula sizes were tested to develop an improved susceptibility method for Malassezia spp. We successfully developed a microdilution broth-based method with considerable advantages over other available methods, and used it for all in vitro susceptibility tests of Malassezia spp. isolates. We report that, on a molar basis, BCO was more effective than fluconazole or itraconazole on most strains of Malassezia spp. isolated from clinical samples (n=29). By contrast, BCO was less effective than itraconazole or terbinafine on the common dermatophytes Trichophyton rubrum and Trichophyton interdigitale. These data place BCO as a promising drug for the treatment of Malassezia-associated skin diseases. Further in vivo studies are now required to ascertain its applicability in the clinical setting.

Examining the Benefits of the Boron-Based Mechanism of Action and Physicochemical Properties of Tavaborole in the Treatment of Onychomycosis.

Onychomycosis is a fungal infection of the nail primarily caused by the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. The topical-based treatment of onychomycosis remains a challenge because of the difficulty associated with penetrating the dense, protective structure of the keratinized nail plate. Tavaborole is a novel small-molecule antifungal agent recently approved in the United States for the topical treatment of toenail onychomycosis. The low molecular weight, slight water solubility, and boron chemistry of tavaborole maximize nail penetration after topical application, allowing for effective targeting of the infection in the nail bed. The efficacy of tavaborole is associated with its novel mechanism of action, whereby it inhibits the fungal leucyl-tRNA synthetase (LeuRS) enzyme. Because LeuRS is an essential component in fungal protein synthesis, inhibition of LeuRS ultimately leads to fungal cell death. Tavaborole is the first boron-based antifungal medication approved for the treatment of mild-to-moderate onychomycosis and presents patients with a new topical option. Previously, ciclopirox and efinaconazole were the only approved topical treatments for onychomycosis. This article details the properties that are at the core of the clinical benefits associated with tavaborole.

Singlet oxygen luminescence kinetics under PDI relevant conditions of pathogenic dermatophytes and molds

A treatment of onychomycosis using the photodynamic effect would be a favorable alternative to currently used antimycotic drugs. This study should be considered as a first step towards development and control of an efficient photodynamic inactivation of onychomycosis causative pathogens. Here, we evaluate the usage of time-resolved 2D singlet oxygen luminescence detection in combination with 2D fluorescence scanning as a tool to understand the behavior of the photosensitizer when applied to fungi on Petri dishes. To investigate the interaction of photosensitizer with fungi in various concentrations and in different stages of live, a photodynamic inactivation was avoided by keeping the samples in darkness. Scans of singlet oxygen luminescence and photosensitizer fluorescence were performed over a period of 24days. Two different photosensitizer, a cationic porphyrin and cationic corrole and two fungi strains, the dermatophyte Trichophyton rubrum and the mold Scopulariopsis brevicaulis, were investigated in this study. The two-dimensional correlation of photosensitizer fluorescence and singlet oxygen luminescence revealed differences in the diffusion of both photosensitizer. Even though the singlet oxygen luminescence was quenched with increasing growth of fungi, it was found that the kinetics of singlet oxygen luminescence could be detected on Petri dishes for both photosensitizers and both fungi strains for up to seven days.

Assessment of Biological Activity and Comparison of UPLC and RP-HPLC Chromatographic Profiles of Clausena excavata Burm.F.

Clausena excavata Burm. F. (Rutaceae) has long been associated with medicinal benefits in folk medicine, particularly in the treatment of cancer and its related disorders in the eastern region of Thailand. In the the present study Ultra Pressure Liquid Chromatography (UPLC) analysis of methanolic leaf extracts of Clausena excavata were carried out using short (5 cm × 2.1 mm I.D.) columns, containing 2 μm particles at very high pressures (up to 16000 psi) to obtain high efficiency separations in very short run times. The results indicate that UPLC provided better resolution compared to routine RP-HPLC. The analysis time was drastically reduced (4 min.) which is proved to be a faster and more economical analytical tool than RP-HPLC. In addition to that, the present study also evaluates anti-fungal activity against dermatophytes Trichophyton rubrum and Trichophyton mentographytes by using an agar incorporation technique. The anti-fungal activity may be due to the presence of Angelecin and gallic acid in the plant extract.

Terbinafine resistance conferred by multiple copies of the salicylate 1-monooxygenase gene in Trichophyton rubrum.

Resistance to antifungals is a leading concern in the treatment of human mycoses. We demonstrate that the salA gene, encoding salicylate 1-monooxygenase, is involved in resistance of the dermatophyte Trichophyton rubrum to terbinafine, one of the most effective antifungal drugs against dermatophytes. A strain with multiple copies of salA was constructed and exhibited elevated expression of salA and increased terbinafine resistance. This reflects a mechanism not yet reported in a pathogenic fungus.

An In Vitro Model for the Study of the Macrophage Response Upon Trichophyton rubrum Challenge.

Diversity in the macrophage models currently employed in immunology studies may lead to opposed results and interpretations. In this study, we aimed to analyze the suitability of J774 macrophage-like cells as a model for the interaction between the dermatophyte Trichophyton rubrum and macrophages. J774 cells were competent in fungal phagocytosis, but succumbed to hyphal growth. Nevertheless, they could also secrete IL-1β in response to the dermatophyte. On the opposite direction, inflammatory, thioglycollate-induced peritoneal macrophages did not succumb to fungal growth and showed no significant IL-1β production. The proteomic profiling of these cells uncovered vimentin and plastin-2 as proteins whose abundance was altered by the fungal interaction. Our study indicates that this cell line could be an interesting tool in the investigation of T. rubrum infection biology.

The physicochemical, safety and antimicrobial properties of Phyllanthus amarus herbal cream and ointment

The ethanol extract of Phyllanthus amarus (Schum and Thonn), a plant of ethnomedicinal importance, was formulated into herbal cream and ointment and evaluated using physicochemical, safety and antimicrobial properties. The extract was obtained by maceration and the antimicrobial properties tested on clinically isolated pathogenic bacteria (Staphylococcus aureus and Pseudomonas aeruginosa) and dermatophytes (Trichophyton rubrum and Candidaalbicans) using established methods. Cream and ointment formulations containing 1–10 % w/w extract was prepared and 4 % w/w humectant (glycerin) was incorporated into the cream while 5 % w/w surfactant (cetomacrogol 1000) was incorporated to the ointment. The results showed that the pH of the formulations was acidic and the viscosity ranged from 1250 to 4950 cP for ointments and 570–1233 cP for creams. The presence of humectant and surfactant significantly (p < 0.05) reduced the viscosities of the formulations. The results of dermal irritation showed negligible irritation index while sub-chronic toxicity tests showed that the formulations did not cause any visible lesions in the skin of the animals after application for twenty-one days. The in vitro antimicrobial properties of formulations were concentration-dependent with the creams showing higher activity. Furthermore, the in vivo activity of the cream on S. aureus showed increased antibacterial activity with increase in extract concentration and humectant presence. The herbal cream and ointment of Phyllanthus amarus extract had acceptable physicochemical and safety profiles with significant (p < 0.05) in vitro and in vivo antimicrobial activity. Thus, the formulations could be useful in the treatment of skin infections instead of using the extract for bathing and rubbing.

Heat Shock Protein 90 (Hsp90) as a Molecular Target for the Development of Novel Drugs Against the Dermatophyte Trichophyton rubrum.

Treatment of fungal infections is difficult due to several reasons, such as side effects of drugs, emergence of resistant strains, and limited number of molecular targets for the drug compounds. In fungi, heat shock proteins (Hsps) have been implicated in several processes with the conserved molecular chaperone Hsp90 emerging as a potential target for antifungal therapy. It plays key cellular roles by eliciting molecular response to environmental changes, morphogenesis, antifungal resistance, and fungal pathogenicity. Here, we evaluated the transcription profiles of hsp genes of the most prevalent dermatophyte Trichophyton rubrum in response to different environmental challenges including nutrient availability, interaction with cells and molecules of the host tissue, and drug exposure. The results suggest that each Hsp responds to a specific stress condition and that the cohort of Hsps facilitates fungal survival under various environmental challenges. Chemical inhibition of Hsp90 resulted in increased susceptibility of the fungus to itraconazole and micafungin, and decreased its growth in human nails in vitro. Moreover, some hsp and related genes were modulated by Hsp90 at the transcriptional level. We are suggesting a role of Hsp90 in the pathogenicity and drug susceptibility of T. rubrum as well as the regulation of other Hsps. The synergism observed between the inhibition of Hsp90 and the effect of itraconazole or micafungin in reducing the fungal growth is of great interest as a novel and potential strategy to treat dermatophytoses.

Superficial Fungal Infections in a French Teaching Hospital in Grenoble Area: Retrospective Study on 5470 Samples from 2001 to 2011.

Superficial fungal infections are predominantly caused by dermatophytes, but the spectrum of species involved is depending on geographic areas and lifestyle. Only few studies have recently described the French epidemiology of these infections, especially dermatophytosis. To determine the epidemiological situation of superficial fungal infections and the spectrum of dermatophytes in Grenoble area. A retrospective study of mycological laboratory records from January 2001 to December 2011 was carried out among patients with suspected fungal infections in the Grenoble University Hospital. Samples (skin scrapings, nail clippings and hair specimens) were collected, and mycological analyses were carried out by conventional methods. A total of 5470 samples collected from 3740 patients were analysed. Among the 1984 (36.3 %) positive cultures, dermatophytes were identified in 1348/1984 (67.9 %) samples, non-dermatophytes in 636/1984 (32.1 %) samples (yeasts 24.4 %, moulds 7.7 %). Toenails and feet were the most frequent localizations collected (2032 samples, 37.1 %, 1181 samples, 21.5 %). These data show the predominance (more than 92.6 %) of anthropophilic dermatophytes (Trichophyton rubrum, Trichophyton interdigitale and Trichophyton tonsurans). Trichophyton rubrum was the most commonly (78.6 %) isolated dermatophyte. Among zoophilic dermatophytes, Trichophyton verrucosum and Microsporum persicolor were regularly isolated.

Sporicidal effect of amorolfine and other antimycotics used in the therapy of fungal nail infections.

Although topical antifungal therapies for treating onychomycosis are available, the cure rate is unsatisfactorily low with a simultaneously high risk of recurrence. One reason might be the formation of dormant fungal cells by the pathogen, known as spores, which can survive in the affected nail keratin, thereby evading the effect of antifungal drugs. In this in vitro study, the ability of amorolfine and four other antimycotics (ciclopirox, bifonazole, terbinafine and fluconazole) to kill microconidia of the dermatophyte Trichophyton rubrum, chlamydospores of the dermatophyte Epidermophyton floccosum and blastospores of the yeast Candida albicans was extensively studied as these fungi occur predominantly in onychomycosis. The effectiveness of all five antimycotics depended on the drug concentration and the incubation time: a concentration of 10-1000 times the minimum inhibitory concentration against growing hyphae cells is needed to exert a sporicidal action. Amorolfine and ciclopirox showed the same sporicidal efficacy and kinetics for all three varieties of spores. Both were more effective than fluconazole and bifonazole against microconidia and chlamydospores as well as slightly more potent against chlamydospores and blastospores than terbinafine after 4 days of incubation and at concentrations of ≥10 μg ml(-1). Finally, sporicidal activity on the tested strains was demonstrated for all five different antimycotics used for onychomycosis treatment.

In vitro model of infected stratum corneum for the efficacy evaluation of poloxamer 407-based formulations of ciclopirox olamine against Trichophyton rubrum as well as differential scanning calorimetry and stability studies

Superficial fungal skin infections are a common disease and concern 20–25% of the world's population with the dermatophyte Trichophyton rubrum being the main trigger. Due to autoinoculation, fungal skin infections of the feet (tinea pedis) often occur simultaneously with fungal nail infections (onychomycosis). Therefore, the overall objective was the development and characterisation of poloxamer 407-based formulations with the antimycotic active ingredient ciclopirox olamine (CPX) for simultaneous antifungal therapy. The formulations consisted of poloxamer 407, water, isopropyl alcohol, propylene glycol and medium chain triglycerides in given ratios. The in vitro antifungal efficacy against T. rubrum was tested in a novel in vitro model of infected stratum corneum in comparison to a marketed semi-solid formulation containing 1% (w/w) ciclopirox olamine and a marketed nail lacquer containing 8% ciclopirox. Several liquid poloxamer 407-based formulations with only 1% CPX completely inhibited fungal growth after 6 days of incubation, whereas the marketed semi-solid formulation did not inhibit fungal growth. Differential scanning calorimetry studies revealing the interaction between the formulations and the SC showed that increasing isopropyl alcohol/propylene glycol concentrations as well as increasing CPX concentrations caused increasing endothermic transition shifts. Moreover, stability studies at 30°C exhibited only a slight decrease of the CPX amount after 12 months of storage. Each formulation contained >90% of the initial CPX concentration after termination of the stability studies.

Effective Single Photodynamic Treatment of ex Vivo Onychomycosis Using a Multifunctional Porphyrin Photosensitizer and Green Light.

Onychomycosis is predominantly caused by the dermatophytes Trichophyton rubrum, Trichophyton mentagrophytes and Trichophyton tonsurans. The main treatment obstacle concerns low nail-plate drug permeability. In vitro antifungal photodynamic treatment (PDT) and nail penetration enhancing effectiveness have been proven for multifunctional photosensitizer 5,10,15-tris(4-N-methylpyridinium)-20-(4-(butyramido-methylcysteinyl)-hydroxyphenyl)-[21H,23H]-porphine trichloride (PORTHE). This study investigates single PORTHE green laser/LED PDT of varying degrees of ex vivo onychomycoses in a human nail model. T. mentagrophytes, T. rubrum, T. tonsurans onychomycoses were ex vivo induced on nail pieces at 28 °C (normal air) and 37 °C (6.4% CO2) during 3 to 35 days and PDTs applied to the 37 °C infections. All dermatophytes showed increasingly nail plate invasion at 37 °C between 7 and 35 days; arthroconidia were observed after 35 days for T. mentagrophytes and T. tonsurans. Using 81 J/cm2 (532 nm) 7-day T. mentagrophytes onychomycoses were cured (92%) with 80 µM PORTHE (pH 8) after 24 h propylene glycol (PG, 40%) pre-treatment and 35-day onychomycoses (52%–67%) with 24 h PORTHE (40–80 µM)/40% PG treatment (pH 5). 28 J/cm2 LED light (525 ± 37 nm) improved cure rates to 72%, 83% and 73% for, respectively, T. mentagrophytus, T. rubrum and T. tonsurans 35-day onychomycoses and to 100% after double PDT. Data indicate PDT relevance for onychomycosis.

Antifungal activity of chitooligosaccharides against the dermatophyte Trichophyton rubrum

Antifungal activity against the dermatophytic fungus Trichophyton rubrum by a well-characterized chitooligosaccharides (COS) sample, hydrolyzed using a recombinant chitosanase, was investigated in vitro and in vivo. The minimum inhibitory concentration (MIC) of COS ranged between 0.25 and 0.50%, which was measured using a microdilution method. Analysis of inhibition rates using an agar diffusion method showed that treatment with 0.5% and 1% COS significantly suppressed T. rubrum cell growth (p<0.05 and p<0.01, respectively, in comparison with untreated control). Morphological changes and structural alterations of cells were observed by TEM. In vivo efficacy of COS in treatment of T. rubrum dermatophytosis was evaluated using a guinea pig model. Skin lesion scores revealed a strong, dose-dependent therapeutic effect of COS. The 5% COS group showed a reduction of skin lesions even greater than that of the positive control group treated with 1% fluconazole (FCZ). Histological analysis revealed no inflammation or tissue destruction in the groups treated with 5% COS or 1% FCZ. Hyperkeratosis was also observed, perhaps resulting from a defensive response of the tissue cells to COS. The findings indicate that COS has excellent potential for development of novel antifungal drugs for clinical treatment/remission of dermatophytoses.

Real-time PCR approach in dermatophyte detection and Trichophyton rubrum identification.

Dermatophytes are keratinophilic molds that infect human hair, nails and skin. Diagnosis of dermatophytosis is based on morphological, serological and biochemical features. However, identification is difficult and laborious due to similarities between microorganisms. Thus, there is considerable interest to develop mycological diagnostic procedures based on molecular biology methods. In this study, fast, two-step DNA extraction method and real-time PCR was used for detection of dermatophytes DNA using pan-dermatophyte primers and identification of Trichophyton rubrum from pure cultures. The applied method allowed correct detection of all dermatophytes and correct identification of Trichophyton rubrum in less than 2 hours.

Tavaborole topical solution, 5% for the treatment of toenail onychomycosis.

Tavaborole topical solution, 5% (tavaborole) is a novel, boron-based, antifungal pharmaceutical agent indicated for treatment of toenail onychomycosis due to the dermatophytes Trichophyton rubrum or Trichophyton mentagrophytes. In preclinical studies, tavaborole effectively penetrated through full-thickness, non-diseased cadaver fingernails, including those with up to four layers of nail polish. Limited systemic absorption was observed following topical application of tavaborole. In phase III clinical trials involving patients with distal subungual onychomycosis affecting 20-60% of a target great toenail, significantly more patients treated with tavaborole versus vehicle achieved completely clear nail with negative mycology following daily application for 48 weeks. Treatment-emergent adverse events reported by at least 1% of patients treated with tavaborole and at a greater frequency versus vehicle included ingrown toenail, exfoliation, erythema and dermatitis. Treatment discontinuations were uncommon. Results from preclinical studies and phase III clinical trials establish tavaborole as a safe and efficacious treatment for toenail onychomycosis.

Trichophyton rubrum DNA strain switching increases in patients with onychomycosis failing antifungal treatments.

The dermatophyte Trichophyton rubrum is responsible for approximately 80% of onychomycosis cases. Genetic strain typing was developed to help elucidate its epidemiology and pathogenicity. To determine T.rubrum DNA strain types in North American patients with onychomycosis and to track the patients before and after their course of treatments. T.rubrum DNA strain types were determined by restriction fragment length polymorphisms in ribosomal DNA and Southern blotting from toenails that were cultured from 50 North American patients with onychomycosis prior to treatment. Some of the patients were subsequently typed from oral terbinafine (n=6), laser (n=9) or placebo (n=8) treatment groups. Three European DNA strains were obtained for comparison. DNA strains from the terbinafine group were tested for in vitro susceptibility to terbinafine. Six DNA strain types (A-F) accounted for 94% of T.rubrum DNA strains and corresponded to European isolates. Three DNA strains (6%) novel to North America were detected. DNA strain type switching occurred in all treatment groups: terbinafine (83%), laser (56%) and placebo (25%). Most of the switches (50%) observed in the terbinafine group coincided with mycological cures followed by relapse. Patients treated with laser therapy or placebo exhibited no intermittent cures. DNA strains from the terbinafine group were all susceptible to terbinafine in vitro. Nine T.rubrum DNA strains were identified in a North American population: three novel and six predominant to a European population. Although DNA strain type switching in onychomycosis is a natural phenomenon, with presence in the placebo group, increases following the course of failed onychomycosis treatment suggest an antifungal-induced response.

In vitro combination therapy using low dose clotrimazole and photodynamic therapy leads to enhanced killing of the dermatophyte Trichophyton rubrum.

BackgroundSuperficial infections of the skin and mucous membranes caused by dermatophyte fungi are amongst the most common and challenging infections to treat. Previously we demonstrated the phototoxic effects of photodynamic therapy (PDT) towards Trichophyton rubrum, using a green laser to photoactivate Rose Bengal (RB). The aim of this study was to evaluate whether we could; (1) achieve a similar effect using an inexpensive light-emitting diode (LED) to photoactivate RB and (2) to evaluate whether our PDT regime could be combined with standard antifungal drug therapy and increase its effectiveness.MethodsWe designed and built our own inexpensive green (530 nm) LED source and tested its efficacy as part our RB-PDT regime in vitro against T. rubrum. We also examined the potential benefits of incorporating PDT as part of combination therapy and whether the order in which this was done had an impact. First we subjected spore suspensions to sub-inhibitory concentrations of a number of antifungal agents (CLT, MCZ and TRB) for 72 hours followed by RB-PDT. Secondly we subjected spore suspensions to sub-inhibitory PDT followed by drug treatment and evaluated if there were any changes to the minimum inhibitory concentrations (MICs) of the drugs tested.ResultsThe optimal conditions for photoinactivation of T. rubrum using RB-PDT alone were 140 μM of RB and 24 J/cm2 of LED (equating to a 30-minute exposure). These parameters also caused a 100% reduction in the viability of the pathogenic yeast Candida albicans and the model fungus Saccharomyces cerevisiae. By combining our RB-PDT regime as an adjunct to antifungal drugs we were able to dramatically reduce the exposure times. Treatment of spore suspensions using a sub-inhibitory dose of clotrimazole (CLT) followed by RB-PDT, this order was critical, significantly reduced the exposure times required to achieve 100% inhibition of T. rubrum to 15 minutes as compared to RB-PDT alone.ConclusionsThe combination of antifungal drug and RB-PDT represents an attractive alternative to the current antifungal therapies used to treat superficial fungal diseases. Our approach has the potential to reduce treatment times and drug dosages which can also reduce drug toxicity and improve patient compliance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-014-0261-z) contains supplementary material, which is available to authorized users.

RNA-sequencing analysis of Trichophyton rubrum transcriptome in response to sublethal doses of acriflavine.

BackgroundThe dermatophyte Trichophyton rubrum is an anthropophilic filamentous fungus that infects keratinized tissues and is the most common etiologic agent isolated in human dermatophytoses. The clinical treatment of these infections is challenging because only few antifungal drugs are commercially available. To understand the mode of action of cytotoxic drugs against fungi, we evaluated the time-dependent effects of acriflavine on T. rubrum transcriptome using high-throughput RNA-sequencing (RNA-seq) technology.ResultsRNA-seq analysis generated approximately 200 million short reads that were mapped to the Broad Institute's Dermatophyte Comparative Database before differential gene expression analysis was performed. By employing a stringent cut-off threshold of −1.5 and 1.5 log2-fold changes in gene expression, a subset of 490 unique genes were found to be modulated in T. rubrum in response to acriflavine exposure. Among the selected genes, 69 genes were modulated at all exposure time points. Functional categorization indicated the putative involvement of these genes in various cellular processes such as oxidation-reduction reaction, transmembrane transport, and metal ion binding. Interestingly, genes putatively involved in the pathogenicity of dermatophytoses were down-regulated suggesting that this drug interferes with the virulence of T. rubrum. Moreover, we identified 159 novel putative transcripts in intergenic regions and two transcripts in intron regions of T. rubrum genome.ConclusionThe results provide insights into the molecular events underlying the stress responses of T. rubrum to acriflavine, revealing that this drug interfered with important molecular events involved in the establishment and maintenance of fungal infection in the host. In addition, the identification of novel transcripts will further enable the improvement of gene annotation and open reading frame prediction of T. rubrum and other dermatophyte genomes.

Antifungal activity of flavonoids and modulation of expression of genes of fatty acid synthesis in the dermatophyte Trichophyton rubrum

Background Dermatophytosis are fungal infections caused by keratinophilic fungi known as dermatophytes and classified in three genera: Trichophyton, Epidermophyton and Microsporum. Trichophyton rubrum is the most frequent species associated to dermatophytosis worldwide [1]. The infections caused by dermatophytes are not lethal, but are difficult to treat and uncomfortable. In the case of T. rubrum, they tend to be chronic, and although the superficial infections are more common, cases of deep infection have been reported in immunocompromised patients [2][3]. The number of antifungal drugs are still limited, and the acquired resistance for some of clinical antifungal have been shown as well as the side effects that have been promoted by them. Reasons for the challenge in development of new antifungal drugs are the similarities shared by fungal and mammalian cells and the lack of knowledge about the biology of these pathogens. Recent evidences have shown that the fatty acid sinthase (FAS) is an interesting antifungal target [4] because of marked differences between human and fungal cells. The aim of this study was to evaluate the antifungal activity of four flavonoids described as FAS inhibitors and verify the modulation of genes in the pathway of fatty acid synthesis in T. rubrum growth in presence of the most effective one as FAS inhibitor.