scholarly journals The Parasexual Cycle in Candida albicans Provides an Alternative Pathway to Meiosis for the Formation of Recombinant Strains

PLoS Biology ◽  
2008 ◽  
Vol 6 (5) ◽  
pp. e110 ◽  
Author(s):  
Anja Forche ◽  
Kevin Alby ◽  
Dana Schaefer ◽  
Alexander D Johnson ◽  
Judith Berman ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Alternative Pathway ◽  
Parasexual Cycle ◽  
Recombinant Strains

scholarly journals A role for complement receptor-like molecules in iron acquisition by Candida albicans.

1992 ◽  
Vol 175 (6) ◽  
pp. 1643-1651 ◽  
Author(s):  
M A Moors ◽  
T L Stull ◽  
K J Blank ◽  
H R Buckley ◽  
D M Mosser
Keyword(s):  
Candida Albicans ◽  
Human Serum ◽  
Iron Acquisition ◽  
Alternative Pathway ◽  
Protoporphyrin Ix ◽  
Surface Proteins ◽  
Pathogenic Potential ◽  
Opportunistic Fungal Pathogen ◽  
Iron Binding Proteins ◽  
Type 3

Candida albicans, an opportunistic fungal pathogen of humans, is dependent upon iron for growth. Consequently, human serum inhibits C. albicans growth due to the presence of high affinity iron-binding proteins that sequester serum iron, making it unavailable for use by the organism. We report that in the inhibitory environment of human serum, the growth of C. albicans can be restored by the addition of exogenous hemoglobin or heme, but not by protoporphyrin IX, the heme precursor that does not contain iron. We further report that C. albicans can utilize cell surface proteins that are homologues of the mammalian complement receptors (CR) to rosette complement-coated red blood cells (RBC) and obtain RBC-derived iron for growth. The ability of Candida to acquire RBC-derived iron under these conditions is dependent upon Candida-RBC rosetting mediated by CR-like molecules. Unopsonized RBC do not support Candida growth in serum, and restoration of Candida growth in serum by complement-opsonized RBC is inhibited by monoclonal antibodies to the human CR type 3 (CR3). In addition, activation of the human alternative pathway of complement by Candida leads to "bystander" deposition of C3 fragments on the surface of autologous, unopsonized RBC, generating the ligands necessary for Candida-RBC rosetting. These results suggest that C. albicans has evolved a unique strategy for acquiring iron from the host, which exploits the host complement system, and which may contribute to the pathogenic potential of the organism.

scholarly journals The Hyphal and Yeast Forms of Candida albicans Bind the Complement Regulator C4b-Binding Protein

2004 ◽  
Vol 72 (11) ◽  
pp. 6633-6641 ◽  
Author(s):  
T. Meri ◽  
A. M. Blom ◽  
A. Hartmann ◽  
D. Lenk ◽  
S. Meri ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Confocal Microscopy ◽  
Binding Site ◽  
Binding Protein ◽  
Alternative Pathway ◽  
Factor H ◽  
Enzyme Linked Immunosorbent Assay ◽  
Classical Pathway ◽  
Pathogenic Yeast ◽  
Yeast Surface

ABSTRACT Candida albicans, an important pathogenic yeast, activates all three pathways of the complement system. To understand how this yeast evades the effects of the activated system, we have analyzed the binding of the classical pathway inhibitor C4b-binding protein (C4BP) by C. albicans. Purified native as well as recombinant C4BP bound dose dependently to the yeast and hyphal forms, as shown by multiple methods, such as confocal microscopy, flow cytometry, a novel enzyme-linked immunosorbent assay, absorption from human serum, and direct binding assays with purified proteins. A prominent binding site was identified at the tip of the germ tube, a structure that is considered important for tissue penetration and pathogenesis. The binding site in C4BP was localized to the two N-terminal complement control protein domains by using recombinant deletion constructs and site-specific monoclonal antibodies. As the alternative pathway inhibitors factor H and FHL-1 also bind to C. albicans, the binding of all three plasma proteins was compared. Simultaneous binding of the classical regulator C4BP and the alternative pathway regulator factor H was demonstrated by confocal microscopy. In addition, FHL-1 competed for binding with C4BP, suggesting that these two related complement regulators bind to the same structures on the yeast surface. The surface-attached C4BP maintains its complement regulatory activities and inactivates C4b. The surface-attached human C4BP serves multiple functions relevant for immune evasion and likely pathogenicity. It inhibits complement activation at the yeast surface and, in addition, mediates adhesion of C. albicans to host endothelial cells.

scholarly journals Influence of Mannan and Glucan on Complement Activation and C3 Binding by Candida albicans

2009 ◽  
Vol 78 (3) ◽  
pp. 1250-1259 ◽  
Author(s):  
Gayle M. Boxx ◽  
Thomas R. Kozel ◽  
Casey T. Nishiya ◽  
Mason X. Zhang
Keyword(s):  
Candida Albicans ◽  
Complement System ◽  
Complement Activation ◽  
Alternative Pathway ◽  
Surface Expression ◽  
Human Neutrophils ◽  
Intact Cells ◽  
Independent Mechanism ◽  
The Complement System ◽  
Wall Components

ABSTRACT The complement system is important for host resistance to hematogenously disseminated candidiasis. However, modulation of complement activation by cell wall components of Candida albicans has not been characterized. Although intact yeast display mannan on the surface, glucan, typically located in the interior, becomes exposed during C. albicans infection. We show here the distinct effects of mannan and glucan on complement activation and opsonophagocytosis. Previous studies showed that intact cells are resistant to initiation of complement activation through the alternative pathway, and antimannan antibody reverses this resistance via an Fc-independent mechanism. The present study shows that this mannan-dependent resistance can be overcome by periodate-borohydride conversion of mannose polysaccharides to polyalcohols; cells treated with periodate-borohydride initiate the alternative pathway without the need for antibody. These observations identify an inhibitory role for intact mannan in complement activation. Next, removal of the surface-displayed mannan by acid treatment of periodate-borohydride cells exposes glucan. Glucan-displaying cells or purified β-glucan initiate the alternative pathway when incubated with the purified proteins of the alternative pathway alone, suggesting that C. albicans glucan is a natural activator of the alternative pathway. Finally, ingestion of mannan-displaying cells by human neutrophils requires anti-mannan antibody, whereas ingestion of glucan-displaying cells requires complement. These results demonstrate a contrasting requirement of natural antibody and complement for opsonophagocytosis of C. albicans cells displaying mannan or glucan. Thus, differential surface expression of mannan and glucan may influence recognition of C. albicans by the complement system.

scholarly journals Characteristics of Fc-independent human antimannan antibody-mediated alternative pathway initiation of C3 deposition to Candida albicans

2009 ◽  
Vol 46 (3) ◽  
pp. 473-480 ◽  
Author(s):  
Gayle M. Boxx ◽  
Casey T. Nishiya ◽  
Thomas R. Kozel ◽  
Mason X. Zhang
Keyword(s):  
Candida Albicans ◽  
Alternative Pathway

scholarly journals Genome-Wide Transcription Profiling of the Early Phase of Biofilm Formation by Candida albicans

2005 ◽  
Vol 4 (9) ◽  
pp. 1562-1573 ◽  
Author(s):  
Luis A. Murillo ◽  
George Newport ◽  
Chung-Yu Lan ◽  
Stefan Habelitz ◽  
Jan Dungan ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Early Stage ◽  
Sulfur Metabolism ◽  
Single Cells ◽  
Alternative Pathway ◽  
Opportunistic Pathogen ◽  
Abiotic Surfaces ◽  
Expression Of Genes ◽  
Structure Changes

ABSTRACT The ability to adhere to surfaces and develop as a multicellular community is an adaptation used by most microorganisms to survive in changing environments. Biofilm formation proceeds through distinct developmental phases and impacts not only medicine but also industry and evolution. In organisms such as the opportunistic pathogen Candida albicans, the ability to grow as biofilms is also an important mechanism for persistence, facilitating its growth on different tissues and a broad range of abiotic surfaces used in medical devices. The early stage of C. albicans biofilm is characterized by the adhesion of single cells to the substratum, followed by the formation of an intricate network of hyphae and the beginning of a dense structure. Changes in the transcriptome begin within 30 min of contact with the substrate and include expression of genes related to sulfur metabolism, in particular MET3, and the equivalent gene homologues of the Ribi regulon in Saccharomyces cerevisiae. Some of these changes are initiated early and maintained throughout the process; others are restricted to the earliest stages of biofilm formation. We identify here a potential alternative pathway for cysteine metabolism and the biofilm-associated expression of genes involved in glutathione production in C. albicans.

scholarly journals Genomic evidence for a hybrid origin of the yeast opportunistic pathogen Candida albicans

2019 ◽  
Author(s):  
Verónica Mixão ◽  
Toni Gabaldón
Keyword(s):  
Candida Albicans ◽  
Opportunistic Pathogen ◽  
Sexual Cycle ◽  
Hybrid Origin ◽  
Species Boundaries ◽  
Compelling Evidence ◽  
Parasexual Cycle ◽  
Evolution Of Virulence ◽  
Vertical Evolution ◽  
Current Species

AbstractOpportunistic yeast pathogens are of increasing medical concern. Candida albicans, the species with the highest incidence, is a natural commensal of humans that can adopt a pathogenic behaviour. This species is highly heterozygous, is an obligate diploid, and cannot undergo meiosis, adopting instead a parasexual cycle. The origin of these traits is unknown and we hypothesize they could result from ancestral hybridization. We tested this idea by analyzing available genomes of C. albicans isolates and comparing them to those of hybrid and non-hybrid strains of other Candida species. Our results show compelling evidence that C. albicans is an evolved hybrid, with levels and patterns of ancestral heterozygosity that cannot be fully explained under the paradigm of vertical evolution. Although the level of inferred divergence between the putative parental lineages (2.8%) is not clearly beyond current species boundaries in Saccharomycotina, we show here that all analyzed C. albicans strains derive from a single hybrid ancestor, which diverged by extensive loss of heterozygosis. This finding has important implications for our understanding of C. albicans evolution, including the loss of the sexual cycle, the origin of the association with humans, and the evolution of virulence traits.

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