ABSTRACT
The incidence of Candida species resistant to traditional antifungal drugs is increasing globally. This issue significantly impacts patients' lives and increases healthcare expenses, confirming the need to develop novel therapeutic strategies. Recently, a thermostable trypsin inhibitor named ShTI (11.558 kDa), which has antibacterial effects on Staphylococcus aureus, was isolated from Salvia hispanica L. (chia) seeds. This study aimed to assess the antifungal effect of ShTI against Candida species and its synergism with fluconazole and to evaluate its mode of action. Preliminary toxicological studies on mouse fibroblasts were also performed. ShTI exhibited antifungal effects against C. parapsilosis (ATCC® 22,019), C. krusei (ATCC® 6258), and six clinical fluconazole-resistant strains of C. albicans (2), C. parapsilosis (2), and C. tropicalis (2). The minimum inhibitory concentration (MIC) values were 4.1 µM (inhibiting 50% of the isolates) and 8.2 µM (inhibiting 100% of the isolates). Additionally, when combined with fluconazole, ShTI had a synergistic effect on C. albicans, altering the morphological structure of the yeast. The mode of action of ShTI against C. krusei (ATCC® 6258) and C. albicans involves cell membrane permeabilization, the overproduction of reactive oxygen species, the formation of pseudohyphae, pore formation, and consequently, cell death. In addition, ShTI (8.65 and 17.3 µM) had noncytotoxic and nongenotoxic effects on L929 mouse fibroblasts. These findings suggest that ShTI could be a promising antimicrobial candidate, but further research is necessary to advance its application as a novel antifungal agent.
Subject(s)
Antifungal Agents , Candida , Drug Resistance, Fungal , Fluconazole , Microbial Sensitivity Tests , Salvia , Seeds , Trypsin Inhibitors , Antifungal Agents/pharmacology , Antifungal Agents/toxicity , Fluconazole/pharmacology , Fluconazole/toxicity , Candida/drug effects , Salvia/chemistry , Seeds/chemistry , Animals , Mice , Trypsin Inhibitors/pharmacology , Plant Extracts/pharmacology , Plant Extracts/chemistry , Fibroblasts/drug effects , Drug Synergism , Candidiasis/microbiology , Candidiasis/drug therapyABSTRACT
Aiming to assess the susceptibility of populations in the Brazilian Amazon region to ionizing radiation emitted from uranium, mutations frequencies in the DNA repair genes XRCC1 and XRCC3 and in the metabolic gene GSTM1 were evaluated. The XRCC1 allele frequencies for the 194Trp polymorphism in the municipalities of Monte Alegre, Prainha and Alenquer were, respectively, 0.12, 0.13 and 0.07, and for 399Gln polymorphism they were, respectively, 0.28, 0.30 and 0.32. Frequencies for GSTM1 gene deletion homozygotes were, respectively, 0.36, 0.31 and 0.40 for all municipalities. These frequencies are comparable to those described for Brazilian individuals from other regions of the country. Also, allele frequencies of XRCC3 241Met polymorphism of the Monte Alegre and Alenquer populations were 0.28 and 0.33, respectively. In conclusion, frequencies of important polymorphic features of cellular DNA repair and metabolic apparatus in the populations studied do not differ from those of populations in other regions of Brazil.
