Serum or bile affects the in vitro azole susceptibilities of Candida spp.

Drug susceptibility tests were performed with a series of Candida spp. in media supplemented with serum or bile. The azole susceptibilities of several medically important Candida spp.

Identification of the putative protein phosphatase gene PTC1 as a virulence-related gene using a silkworm model of Candida albicans infection.

Protein phosphatases are critical for the regulation of many cellular processes. Null mutants of 21 putative protein phosphatases of Candida albicans were constructed by consecutive allele replacement using the URA3 and ARG4 marker genes. A simple silkworm model of C.

Inhibition of fungal ABC transporters by unnarmicin A and unnarmicin C, novel cyclic peptides from marine bacterium.

Novel inhibitors of fungal ATP-binding cassette transporters were obtained by screening compounds and crude extracts from marine-derived fungi and bacteria using disk diffusion assays of Saccharomyces cerevisiae strains overexpressing a variety of fungal multi-drug efflux pumps. The cyclodepsipeptides unnarmicin A and unnarmicin C were able to sensitize cells overexpressing azole drug pumps ScPdr5p, CaCdr1p, CgCdr1p, and CgPdh1p to sub-MIC concentrations of fluconazole without affecting the growth of CaCdr2p and CaMdr1p overexpressing cells. Unnarmicin A and unnarmicin C were potent inhibitors of rhodamine 6G efflux of CaCdr1p expressing cells with IC50 values of 3.

The Candida glabrata putative sterol transporter gene CgAUS1 protects cells against azoles in the presence of serum.

Objectives: The uptake of endogenous sterol from serum may allow Candida glabrata to survive azole treatment. This study aims to determine the contribution of a sterol transporter that alters fluconazole sensitivity in the presence of serum.

Methods: Bioinformatic analysis predicted CgAUS1 as the C.

Contribution of the myeloperoxidase-dependent oxidative system to host defence against Cryptococcus neoformans.

The in vivo contribution of reactive oxygen species produced by neutrophils against Cryptococcus infection is not widely recognized. Myeloperoxidase (MPO) is a neutrophil-specific enzyme that catalyses the production of hypohalous acids such as HOCl from H2O2. This study investigated the role of MPO in immunological defence against Cryptococcus neoformans in an MPO-deficient (MPO-/-) mouse model.

Functional analysis of fungal drug efflux transporters by heterologous expression in Saccharomyces cerevisiae.

Clinically important resistance of fungal pathogens to azole antifungal drugs is most frequently caused by the over-expression of energy-dependent drug efflux pumps. These pumps usually belong to either the ATP-binding cassette (ABC) family or the Major Facilitator Superfamily (MFS) class of membrane transporter. Little is known about how these pumps work and there is an urgent need to develop pump antagonists that circumvent azole resistance.

Candida albicans protein kinase CaHsl1p regulates cell elongation and virulence.

Saccharomyces cerevisiae Hsl1p is a Ser/Thr protein kinase that regulates cell morphology. We identified Candida albicans CaHSL1 and analysed its function in C. albicans.

In vivo role of myeloperoxidase for the host defense.

Myeloperoxidase (MPO) is located within neutrophils capable of producing HOCl. To define the in vivo role of MPO, we have generated MPO-knockout (MPO-KO) mice. The mice without MPO developed normally.

Regulated overexpression of CDR1 in Candida albicans confers multidrug resistance.

Objectives: Information on the function of Candida albicans ATP-binding cassette (ABC) membrane transporter Cdr1p has come from studying the effect of gene inactivation in C. albicans and from heterologous Cdr1p expression in the yeast Saccharomyces cerevisiae. These approaches, however, give only an indirect indication of Cdr1p function in C.

Critical role of myeloperoxidase and nicotinamide adenine dinucleotide phosphate-oxidase in high-burden systemic infection of mice with Candida albicans.

Oxygen metabolites generated by myeloperoxidase (MPO) and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase contribute to microbial killing by phagocytes. To compare the importance of the 2 enzymes for host defense, MPO-deficient (MPO(-/-)) mice and NADPH-oxidase-deficient mice with chronic granulomatous disease (CGD mice) were intraperitoneally infected with 3 different doses of Candida albicans, and their infection severity was analyzed. CGD mice had increased mortality and exhibited increased tissue fungal burden in a dose-dependent manner, whereas normal mice showed no symptoms.