Phenolic Composition, Toxicity Potential, and Antimicrobial Activity of Licania rigida Benth (Chrysobalanaceae) Leaf Extracts.

This study was conducted to evaluate the phenolic composition, toxicity, and antimicrobial activity of Licania rigida Benth, an underexploited wild Licania species. L. rigida leaf fractions (ethyl alcohol and ethyl acetate) were analyzed for their phenolic compound and flavonoid total, and high-performance liquid chromatography/ultraviolet spectra chromatographic profiles. Regarding the extract biological effects, toxicity was measured by acute oral toxicity in Wistar rats, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] method, and apoptosis indicators with DAPI in VERO cells, whereas well-agar diffusion and broth microdilution assays were applied to evaluate the antimicrobial ability. The phytochemical analysis resulted in significant amounts of phenolic compounds and total flavonoids in the extract and fraction, with flavonol-3-O-glycosylates as the main constituent. Regarding the extract and fraction antimicrobial activity, the results showed a significant effect against gram-positive bacteria and fungi, among which Staphylococcus epidermidis and Candida krusei displayed more susceptibility. No toxicity effects were observed in animals. Concerning the cytotoxicity assay, only the highest dose tested exhibited a minimal toxic effect on the analyzed cell lines. These results are relevant considering the increase of multiresistant microorganisms to conventional treatments applied. Therefore, investigating the pharmacological properties of the genus Licania is promising in the search for new sources of antimicrobial compounds.

Comparison of Cryptococcus gattii/neoformans Species Complex to Related Genera (Papiliotrema and Naganishia) Reveal Variances in Virulence Associated Factors and Antifungal Susceptibility.

Cryptococcosis is an infectious disease of worldwide distribution, caused by encapsulated yeasts belonging to the phylum Basidiomycota. The genus Cryptococcus includes several species distributed around the world. The C. gattii/neoformans species complex is largely responsible for most cases of cryptococcosis. However, clinical series have been published of infections caused by Papiliotrema (Cryptococcus) laurentii and Naganishia albida (Cryptococcus albidus), among other related genera. Here, we examined the pathogenic potential and antifungal susceptibility of C. gattii/neoformans species complex (clades I and II) and related genera (Papiliotrema and Naganishia) isolated from environmental and clinical samples. P. laurentii (clade III), N. liquefasciens/N. albidosimilis (clade IV); and N. adeliensis/N. albida (clade V) strains produced higher levels of phospholipase and hemolysins, whereas the C. gattii/neoformans species complex strains (clades I and II) had markedly thicker capsules, produced more biofilm biomass and melanin, which are known virulence attributes. Interestingly, 40% of C. neoformans strains (clade II) had MICs above the ECV established for this species to amphotericin B. Several non-C. gattii/neoformans species complex (clades III to V) had MICs equal to or above the ECVs established for C. deuterogattii and C. neoformans for all the three antifungal drugs tested. Finally, all the non-C. gattii/neoformans clinical isolates (clades III to V) produced more melanin than the environmental isolates might reflect their particularly enhanced need for melanin during in vivo protection. It is very clear that C. gattii/neoformans species complex (clades I and II) strains, in general, show more similar virulence phenotypes between each other when compared to non-C. gattii/neoformans species complex (clades III to V) isolates. These observations together with the fact that P. laurentii and Naganishia spp. (clades III to V) strains were collected from the outside of a University Hospital, identify features of these yeasts important for environmental and patient colonization and furthermore, define mechanisms for infections with these uncommon pathogens.

Exploring the resistance mechanisms in Trichosporon asahii: Triazoles as the last defense for invasive trichosporonosis.

Trichosporon asahii has recently been recognized as an emergent fungal pathogen able to cause invasive infections in neutropenic cancer patients as well as in critically ill patients submitted to invasive medical procedures and broad-spectrum antibiotic therapy. T. asahii is the main pathogen associated with invasive trichosporonosis worldwide. Treatment of patients with invasive trichosporonosis remains a controversial issue, but triazoles are mentioned by most authors as the best first-line antifungal therapy. There is mounting evidence supporting the claim that fluconazole (FLC) resistance in T. asahii is emerging worldwide. Since 2000, 15 publications involving large collections of T. asahii isolates described non-wild type isolates for FLC and/or voriconazole. However, very few papers have addressed the epidemiology and molecular mechanism of antifungal resistance in Trichosporon spp. Data available suggest that continuous exposure to azoles can induce mutations in the ERG11 gene, resulting in resistance to this class of antifungal drugs. A recent report characterizing T. asahii azole-resistant strains found several genes differentially expressed and highly mutated, including genes related to the Target of Rapamycin (TOR) pathway, indicating that evolutionary modifications on this pathway induced by FLC stress may be involved in developing azole resistance. Finally, we provided new data suggesting that hyperactive efflux pumps may play a role as drug transporters in FLC resistant T. asahii strains.