Efeito do butirato de sódio sobre células planctônicas e sésseis de Trichosporon asahii e T.inkin

Abstract

Species of Trichosporon are known to cause superficial infections, such as white piedra. However, this fungus has been prominent in recent decades in invasive and disseminated infections in immunocompromised patients. When fungal cells associate, forming biofilms in medical devices, the clinical condition worsens, with the occurrence of resistance to various antifungal agents. Thus, the need to research new control strategies led to an alternative: sodium butyrate (NaBut), a histone deacetylase inhibitor that can alter chromatin conformation. This inhibitor has been used to modulate epigenetic states, presenting an expressive effect on the decrease of the expression of virulence factors and changes in the growth of pathogenic fungi, such as Cryptococcus spp. and Candida spp. The objective of this study was to investigate the effects, in vitro, of the sodium butyrate over the growth, morphology and sensitivity to antifungal of clinical strains of T. asahii (n = 3) and T. inkin (n = 7), belonging to the Collection of Cultures of the Specialized Center in Medical Mycology (SCMM), Faculty of Medicine, Federal University of Ceará. All samples were recovered in Potato Agar Dextrose, incubated at 35 ° C for 48 h. The cultures were evaluated for in vitro susceptibility to NaBut and to antifungal agents for therapeutic use in planktonic cells and associated in biofilms. The occurrence of the interaction effect between NaBut and antifungal against strains of Trichosporon spp. were also evaluated. Additionally, the action of NaBut on the morphology of Trichosporon species was analyzed. All tests were performed in triplicate, and the results were statistically evaluated by test of varianceANOVA, Bonferroni post-test, Kruskal-Wallis test and Dunn post-test to compare the values found (p <0.05). NaBut inhibited the growth of planktonic cells by 50% at concentrations of 60 mM and 120 mM. In biofilms, at the adhesion phase, there was a reduction in metabolic activity of 10% (MIC) and 45% (10x MIC), on average.At the forming stage, the reduction in metabolic activity was 25% (MIC) and 63% (10x MIC).Also in this phase, the biomass decreased by 45% (MIC) and 81% (10x MIC). In mature biofilm, a decrease of 18% in metabolic activity (MIC) and 48% (10x MIC) was observed, as well as biomass reduction in 51% (MIC) and 77% (10x MIC). In the drug interaction test, NaBut enhanced the effect of most of the antifungal agents tested, in vitro, in planktonic cells and in biofilms.NaBut altered the morphology of Trichosporon spp, reducing filamentation in planktonic cells and de-structured biofilms. Therefore, NaBut has antifungal activity and the potential to inhibit pathogenic species of this emerging fungus.