Lycorine Hydrochloride Inhibits the Virulence Traits ofCandida albicans

The human opportunistic fungal pathogenCandida albicanscauses a severe health burden while the biofilms formed byC. albicanspresent a kind of infections that are hard to cure, highlighting the pressing need for new antifungal drugs againstC. albicans. This study was to explore the antifungal activities of lycorine hydrochloride (LH) againstC. albicans. The minimal inhibitory concentration (MIC) of LH againstC. albicansSC5314 was 64μM. Below its MIC, LH demonstrated antivirulence property by suppressing adhesion, filamentation, biofilm formation, and development, as well as the production of extracellular phospholipase and exopolymeric substances (EPS). The cytotoxicity of LH against mammalian cells was low, with half maximal inhibitory concentrations (IC50) above 256μM. Moreover, LH showed a synergistic effect with AmB, although its interaction with fluconazole, as well as caspofungin, was indifferent. Thus, our study reports the potential use of LH, alone or in combination with current antifungal drugs, to fightC. albicansinfections.

Roles of the Transcription Factors Sfl2 and Efg1 in White-Opaque Switching in a/α Strains ofCandida albicans

ABSTRACTCandida albicansremains the most pervasive fungal pathogen colonizing humans. The majority of isolates from hosts are heterozygous at the mating type locus (MTLa/α), and a third of these have recently been shown to be capable of switching to the opaque phenotype. Here we have investigated the roles of two transcription factors (TFs) Sfl2 and Efg1, in repressing switching ina/α strains. Deleting either gene results in the capacity ofa/α cells to switch to opaque en masse under facilitating environmental conditions, which includeN-acetylglucosamine (GlcNAc) as the carbon source, physiological temperature (37°C), and high CO2(5%). These conditions are similar to those in the host. Our results further reveal that while glucose is a repressor ofsfl2Δ andefg1Δ switching, GlcNAc is an inducer. Finally, we show that when GlcNAc is the carbon source, and the temperature is low (25°C), theefg1Δ mutants, but not thesfl2Δ mutants, form a tiny, elongate cell, which differentiates into an opaque cell when transferred to conditions optimal fora/α switching. These results demonstrate that at least two TFs, Sfl2 and Efg1, repress switching ina/α cells and thata/α strains with either ansfl2Δ orefg1Δ mutation can switch en masse but only under physiological conditions. The role of opaquea/α cells in commensalism and pathogenesis must, therefore, be investigated.IMPORTANCEMore than 95% ofCandida albicansstrains isolated from humans areMTLa/α, and approximately a third of these can undergo the white-to-opaque transition. Therefore, besides being a requirement forMTL-homozygous strains to mate, the opaque phenotype very likely plays a role in the commensalism and pathogenesis of nonmating,a/α populations colonizing humans.

Dioscin Inhibits Virulence Factors ofCandida albicans

Candida albicansinfections present a heavy burden upon public health, with only a few drugs available, while biofilms formed byC. albicansworsen this situation. Dioscin has antitumor, anti-inflammatory, and hepatoprotective effects, and this study was conducted to evaluate the effects of dioscin on the biofilm formation and development, as well as other virulence factors ofC. albicanssuch as morphological transition, adhesion, and extracellular secreted phospholipase. Our results showed dioscin inhibits these virulence factors and has low cytotoxicity against mammalian cells. Considering protective effects of dioscin against damage on liver and kidney, dioscin may be used as a potential candidate for antifungal development.

Antibiotic-induced decreases in the levels of microbial-derived short-chain fatty acids promote gastrointestinal colonization ofCandida albicans

ABSTRACTCandida albicansis the fourth most common cause of systemic nosocomial infections, posing a significant risk in immunocompromised individuals. As the majority of systemicC. albicansinfections stem from endogenous gastrointestinal (GI) colonization, understanding the mechanisms associated with GI colonization is essential in the development of novel methods to preventC. albicans-related mortality. In this study, we investigated the role of microbial-derived short-chain fatty acids (SCFAs) including acetate, butyrate, and propionate on growth, morphogenesis, and GI colonization ofC. albicans. Our results indicate that cefoperazone-treated mice susceptible toC. albicansinfection had significantly decreased levels of SCFAs in the cecal contents that correlate with a higher fungal load in the feces. Further, usingin vivoconcentration of SCFAs, we demonstrated that SCFAs inhibit the growth, germ tube, hyphae and biofilm development ofC. albicans in vitro. Collectively, results from this study demonstrate that antibiotic-induced decreases in the levels of SCFAs in the cecum enhances the growth and GI colonization ofC. albicans.

Rare presentation ofCandida albicans: infective endocarditis and a pulmonary coin lesion

We present a case of a rare association of infective endocarditis and a coin lesion in the lung caused byCandida albicans. The lesion disappeared after 6 weeks of treatment with 5 mg/kg/day amphotericin B.