The yeast Candida albicans binds complement regulators factor H and FHL-1

The human facultative pathogenic yeast Candida albicans causes mucocutaneous infections and is the major cause of opportunistic fungal infections in immunocompromised patients. C. albicans activates both the alternative and classical pathway of the complement system. The aim of this study was to assay whether C. albicans binds human complement regulators in order to control complement activation at its surface. We observed binding of two central complement regulators, factor H and FHL-1, from normal human serum to C. albicans by adsorption assays, immunostaining, and fluorescence-activated cell sorter (FACS) analyses. Specificity of acquisition was further confirmed in direct binding assays with purified proteins. The surface-attached regulators maintained their complement regulatory activities and mediated factor I-dependent cleavage of C3b. Adsorption assays with recombinant deletion mutant proteins were used to identify binding domains. Two binding sites were localized. One binding domain common to both factor H and FHL-1 is located in the N-terminal short consensus repeat domains (SCRs) 6 and 7, and the other one located in C-terminal SCRs 19 and 20 is unique to factor H. These data indicate that by surface acquisition of host complement regulators, the human pathogenic yeast C. albicans is able to regulate alternative complement activation at its surface and to inactivate toxic complement activation products.     

Signaling the glycoshield: maintenance of the Candida albicans cell wall

In fungi, the cell wall is a scaffold, an armor and an environmental gate. Sugar polymers including protein-O- or N-linked glycosyl chains or polysaccharides such as glucan or chitin are essential components to maintain cell wall functions. We describe mechanisms in the human fungal pathogen Candida albicans, by which the integrity of glycostructures are sensed and regulated. The results stress the importance of membrane sensors and MAP kinase pathways in the maintenance of cell wall structure and function.     

Candida albicans and selenium

Although low selenium levels have been recorded in infants, no specific human disorder has been linked to low selenium status. The incidence of thrush, the common enteric fungal infection caused by Candida albicans, has increased markedly with antibiotic therapy and research has provided evidence that its colonization leads to competition for Coenzyme Q10 (CoQ10) in the host. Furthermore it is now known that ubiquinones are essential in heart muscle for oxidative phosphorylation in the mitochondrial respiratory chain and considered that glutathione peroxidase (GSHPx) in the mitochondria protects ubiquinone from oxidation.     

Morphogenesis in Candida albicans

This review will survey environmental controls on the morphology of Candida albicans, describe the cellular and ultrastructural events associated with morphological transitions in this fungus, and attempt to relate biochemical phenomena that have been reported to be associated with dimorphic change to C. albicans cell biology. The synthesis of the cell wall of C. albicans and its control remain largely undiscovered, but it is clear that the cell wall is the principal component involved in shape determination. Possible models for C. albicans dimorphism will be critically reviewed.     

Purification of actin from Candida albicans and comparison with the Candida 48,000-Mr protein.

Actin was purified from Candida albicans cells by affinity chromatography by DNase-Sepharose and was recognized by immunoblotting with monoclonal antibody directed against chick muscle actin. The C. albicans 48-kilodalton protein recognized by sera from patients with invasive candidiasis was shown by DEAE chromatography and immunoblotting not to be identical with the purified C. albicans actin.     

A standardized densitometric immunoblotting analysis of Candida albicans protein allergens

Sera from 196 patients with a strong skin reactivity to Candida albicans and a history of atopic disease were used for C. albicans IgE-immunoblotting. The IgE-immunoblots were analysed by densitometry and integration of the densitogram peaks. A standardized reference disc system allowed parallel analysis of several different immunoblotting experiments. Altogether 105 patients had C. albcans specific IgE antibodies in immunoblotting. The IgE-response against C. albicans was extremely polyspecific and was directed against 42 different bands. The most important IgE binding bands were 46 kDa and 27 kDa bands against which 44 (42%) and 29 (28%) patients, respectively, had IgE responses. A combination of IgE-immunoblotting and densitometry was found practical in analysis of large number of patient sera allowing a profound and accurate analysis and characterization of C. albicans allergen extract. This data evolved from a sufficiently large patient population can be utilized in further standardization of C. albicans extracts.     

Candida albicans and atopic dermatitis

The role of sensitization and exposure to Candida albicans in atopic dermatitis (AD) was studied with skin-prick tests, yeast cultures and immunoblotting in 156 young adults with AD attending the Department of Dermatology, University of Turku, during 1983–89. Eighteen patients with allergic rhinitis without eczema and 39 non-atopics were included as controls. Parameters associated with severe AD were simultaneous anti-C. albicans IgE and saprophytic C. albicans growth. A statistically significant correlation between C. albicans sensitization (specific IgE antibodies) and AD symptoms was observed only in patients with saprophytic C. albicans exposure. No correlation between C. albicans-specific IgE and AD severity was shown in patients without gastrointestinal growth. Furthermore, severe eczema was seldom seen in patients without saprophytic C. albicans growth. The most important IgE-binding components of C. albicans in immunoblotting were 27 and 46 kD proteins and mannan, a polysaccharide. IgG and IgA antibodies to C. albicans, mainly towards C. albicans mannan, were found in practically all 70 sera studied. These results suggest a continuous exposure and induction of IgE antibodies by C. albicans in AD patients. Severe phases of AD in colonized patients are associated with IgE synthesis against C. albicans. These findings suggest a role for C. albicans in the exacerbations of AD but the clarification of this subject needs double-blind placebo-controlled treatment trials.     

Myosin-activating protein kinases are possible regulators of nonmuscle myosin in developing human heart

We studied the localization of myosin-activating protein kinases in cardiomyocytes obtained from fetal human heart at 8–9 weeks gestation. It was found that at this developmental stage, smooth muscle/nonmuscle myosin light chain kinase (MLCK, 108 kDa) and its high-molecular weight isoform (MLCK, 210 kDa), skeletal MLCK and death-associated protein kinase (DAPK) are co-localized with nonmuscle myosin IIB in the premyofibrils. The data obtained suggest that cardiac nonmuscle myosin at 8–9 weeks gestation may serve as the substrate of the studied myosin-activating protein kinases that are likely to cooperatively regulate the formation of myofibrils. We revealed high-molecular weight isoform of smooth muscle/nonmuscle kinase MLCK-210 in developing human heart and determined the ratios of MLCK-108 and MLCK-210 at different gestational stages. In this case, the approximate time period of changes in these isoforms ratio was revealed (between 8–9 and 13 weeks), that can be associated with functional changes in the developing myocardium.     

Amplification of the hyphal wall protein 1 gene to distinguish Candida albicans from Candida dubliniensis

The authors developed a new, simple, and reliable PCR/restriction fragment length polymorphism technique, using amplification of the hyphal wall protein 1 gene of Candida albicans and its gene homologue in Candida dubliniensis, to differentiate the two species of Candida. Performed with a new primer set, CRR-f/CRR-r, PCR produced two different fragments: one of 1,180 bp for C. albicans, and one of 930 bp for C. dubliniensis.     

Heterogeneous surface distribution of the fibrinogen-binding protein on Candida albicans.

As detected by indirect immunofluorescence and confocal microscopy, fibrinogen binding was heterogeneously distributed on the surface of Candida albicans. A low level of binding was generally observed homogeneously distributed on some yeast and most hyphal extensions of germ tubes. However, on most hyphal extensions, there were randomly distributed areas of increased expression, as revealed by patches of greater fluorescence intensity.     

Natural auxotrophic heterozygosity in Candida albicans

Candida albicans is imperfect and diploid. This unusual genetic state permits the occurrence of strains heterozygous for recessive deleterious alleles. These alleles can be brought to homozygosity and therefore expression by UV irradiation-induced mitotic crossing over. Heterozygosity for recessive auxotrophic alleles is found in 10 to 15% of the strains. A wide variety of auxotrophic alleles have been found in such natural heterozygotes but one type, termed Suf +/- was found at an unusually high frequency. Some 5 to 10% of strains are of the Suf +/- type. Suf- homozygous auxotrophs are defective in sulfite reductase. Such auxotrophs require a source of reduced sulfur such as methionine or cysteine, alternatively inorganic thiosulfate will serve as a supplement. Complementation analysis of a variety of Suf- auxotrophs established that 11 out of 12 strains were in a single complementation group.     

TAC1在白念珠菌对抗真菌药物产生耐药性中的作用

由于器官移植患者大量使用免疫抑制剂、癌症患者长期接受放化疗以及广谱抗生素的滥用和艾滋病的广泛传播，免疫功能低下者人数不断增多，真菌感染发生率逐年增加，尤其是白念珠菌（Candida albicans）感染最为常见。三唑类药物氟康唑是治疗念珠菌感染的常用药物，长期用药和重复给药往往会引起耐药现象，最终导致治疗失败。目前已经明确的白念珠菌的耐药机制主要包括：     

Candida albicans,plasticity and pathogenesis

Abstract

The yeast Candida albicans has emerged as a major public health problem during the past two decades. The spectrum of diseases caused by this species ranges from vaginal infections, which affect up to 75% of the women at least once in their lifetime, to deep infections in hospitalized patients which lead to high morbidity and mortality rates. Candida albicans may also play a role in the persistence or worsening of some chronic inflammatory bowel diseases. Active research is now improving our understanding of the molecular mechanisms and genetic factors in the yeast and its host which influence the development of disease. Despite these advances and the availability of a more extensive therapeutic arsenal, current progress in the control of nosocomial infections due to Candida remains limited, mainly due to the difficulties in diagnosing these infections. The biologist has a key role to play in establishing a dialogue with the clinician in order to identify the saprophyte/pathogen transition in patients as early as possible. This review provides a quick synopsis of the modern concepts of Candida pathogenesis with some representative examples illustrating the specifics traits of this yeast in terms of pathogenic adaptation.     

UV-induced instability in Candida albicans hybrids

Summary Auxotrophic variants were obtained following UV-irradiation of Candida albicans hybrids which were heterozygous (+/+/-/-/) for various genetic markers (met, ade, his, lys). Some variants contained less DNA (per cell) than did the hybrids from which they originated; such variants were considered to arise in a process which resulted in generalized reduction in ploidy. These results provide the basis for a cyclic parasexual system (2n × 2n 4n 2n) for genetic analysis in this amictic diploid species.