Trichophyton rubrum is responsible for several superficial human mycoses. Novel strategies aimed at controlling this pathogen are being investigated. The objective of this study was to evaluate the antifungal activity of the antidepressant sertraline (SRT), either alone or in combination with caspofungin (CASP). We calculated the minimum inhibitory concentrations of SRT and CASP against T. rubrum. Interactions between SRT and CASP were evaluated using a broth microdilution chequerboard. We assessed the differential expression of T. rubrum cultivated in the presence of SRT or combinations of SRT and CASP. We used MTT and violet crystal assays to compare the effect of SRT alone on T. rubrum biofilms with that of the synergistic combination of SRT and CASP. A human nail infection assay was performed. SRT alone, or in combination with CASP, exhibited antifungal activity against T. rubrum. SRT targets genes involved in the biosyntheses of cell wall and ergosterol. Furthermore, the metabolic activity of the T. rubrum biofilm and its biomass were affected by SRT and the combination of SRT and CASP. SRT alone, or in combination, shows potential as an approach to minimise resistance and reduce virulence.

No abstract

The dermatophyte Trichophyton rubrum is responsible for most human cutaneous infections. Its treatment is complex, mainly because there are only a few structural classes of fungal inhibitors. Therefore, new strategies addressing these problems are essential. The development of new drugs is time-consuming and expensive. The repositioning of drugs already used in medical practice has emerged as an alternative to discovering new drugs. The antidepressant sertraline (SRT) kills several important fungal pathogens. Accordingly, we investigated the inhibitory mechanism of SRT in T. rubrum to broaden the knowledge of its impact on eukaryotic microorganisms and to assess its potential for future use in dermatophytosis treatments. We performed next-generation sequencing (RNA-seq) to identify the genes responding to SRT at the transcript level. We identified that a major effect of SRT was to alter expression for genes involved in maintaining fungal cell wall and plasma membrane stability, including ergosterol biosynthetic genes. SRT also altered the expression of genes encoding enzymes related to fungal energy metabolism, cellular detoxification, and defense against oxidative stress. Our findings provide insights into a specific molecular network interaction that maintains metabolic stability and is perturbed by SRT, showing potential targets for its strategic use in dermatophytosis.

This study aimed to investigate the effect of the n-butanol fraction of Terminalia catappa Linn., (FBuTC) on biofilm of Candida albicans and Candida glabrata, as well as changes in color and roughness of polymethyl methacrylate resin (PMMA). The susceptibility of C. albicans and C. glabrata to FBuTC was evaluated by means of the Minimum Inhibitory and Minimum Fungicidal Concentration (MIC and MFC). PMMA acrylic resin discs (N= 108) were fabricated. For the susceptibility tests, biofilms of C. albicans and C. glabrata were developed on discs for 48 h and immersed in phosphate-saline buffer solution (PBS), 1% sodium hypochlorite (SH 1%), or FBuTC at MIC, 5xMIC, or 10xMIC. For the color and roughness change tests, the discs were immersed in distilled water, SH 1%, or FBuTC in the concentrations of 0.25 mg/mL, 2.5 mg/mL, or 25.0 mg/mL. After 28 days of incubation, color change was evaluated by spectrophotometry and roughness, by using a profilometer. The biofilms were investigated by one-way ANOVA and, the color and roughness changes (two-way ANOVA and the Tukey test; α=0.05). For both MIC and MFC the value of 0.25 mg/mL of FBuTC was observed for the planktonic cells of C. albicans and C. glabrata. Exposure to FBuTC at 10xMIC had a significant effect on the biofilm of C. albicans, showing a reduction in cell counts when compared with PBS, (p=0.001). For the biofilm of C. glabrata, the MIC was sufficient for significantly reducing the cell count (p<0.001). No important changes in color and roughness of the acrylic resin were observed, even after 28 days, irrespective of the concentration of FBuTC used (p >0.05). It could be concluded that the immersion of acrylic resin for dental prosthesis in FBuTC was effective in reducing the biofilms of C. albicans and C. glabrata without evidence of change in roughness and color of this substrate.

Resumo. Objetivos: Considerado a importância dos biofilmes, o presente trabalho teve como objetivo avaliar as características da comunidade bacteriana existente em biofilmes associados a superfície de torneiras dispensadoras de água potável.  Material e métodos: As amostras foram coletadas na abertura das torneiras, células foram semeadas, contadas e submetidas a coloração de Gram, testes de assimilação de carbono (BIOLOG) e Rugai. Resultados: Com o presente trabalho foi possível visualizar tanto bactérias Gram-positivas quanto negativas e quantificar as unidades formadoras de colônias por swab (UFC/Swab) encontradas em cada dispersador de água potável. Conclusões: As bactérias encontradas utilizam diversas fontes de carbono disponíveis para produção de nutrientes que neceita para sua sobrevivência, o método escolhido foi eficiente para classificação das bactérias encontradas.

Resumo. Objetivos: verificar a produção enzimática e a capacidade de aderência e formação de biofilme em isolados clínicos de Candida tropicalis. Material e métodos: 14 isolados provenientes de amostras clínicas obtidas de um laboratório particular de São Luís- MA, foi realizada a identificação pelo sistema automatizado VITEK (bio Mérieux). Resultados: Todos os isolados foram aderentes ao vidro e a maioria apresentou aderência moderada, 42,9% foram positivas para proteinases, 78,6% para fosfolipases, com Pz variando de 0,47 a 0,9. Todos os isolados apresentaram atividade hemolítica em meio sólido e sete isolados mostraram IH ≥ 2.0. Conclusões: Os isolados de Candida tropicalis avaliados foram capazes de aderir a superfícies inertes com padrões distintos de organização celular, onde alguns destes tipos poderiam facilitar a formação de biofilmes por estas espécies, a propriedade de aderência não está diretamente relacionada ao sítio de infecção, mas provavelmente com fatores específicos destes microrganismos e com a resposta do hospedeiro.

O objetivo principal deste trabalho foi avaliar o perfil de susceptibilidade de isolados clínicos de Candida glabrata através da técnica de difusão em ágar a uma fração extraída com n-butanol das folhas de Terminalia catappa (F-OHf), comparando este tratamento com um outro realizado com o antifúngico de uso clínico e tradicional, o fluconazol (FCZ). A F-OHf apresentou atividade inibitória contra os isolados de C. glabrata, as zonas de inibição de crescimento variaram entre 19 a 27 mm para o tratamento com 40 mg/mL e entre 24 a 31 mm para a concentração 100 mg/mL, para o FCZ as zonas de inibição variaram de 0 a 5 mm. Em sua totalidade, F-OHf pode ser uma alternativa promissora para o tratamento da candidíase, estes resultados representam novas perspectivas para futuras pesquisas em continuação a este estudo para desenvolver terapias alternativas no combate destas infecções.

Title: Synergism between Fluconazole and Terminalia catappa Extract and its Use in the Treatment of Candida-infected Tenebrio molitor Larvae Título: Sinergismo entre Fluconazol e o Extrato de Terminalia catappa e seu uso no tratamento de larvas de Tenebrio molitor infectadas com Candida