biofilms resist the effects of available antifungal therapies. Prior studies with biofilms show that an extracellular matrix mannan-glucan complex (MGCx) contributes to antifungal sequestration, leading to drug resistance. Here we implement biochemical, pharmacological, and genetic approaches to explore a similar mechanism of resistance for the three most common clinically encountered non- species (NAC). Our findings reveal that each species biofilm synthesizes a mannan-glucan complex and that the antifungal-protective function of this complex is conserved. Structural similarities extended primarily to the polysaccharide backbone (α-1,6-mannan and β-1,6-glucan). Surprisingly, biochemical analysis uncovered stark differences in the branching side chains of the MGCx among the species. Consistent with the structural analysis, similarities in the genetic control of MGCx production for each species also appeared limited to the synthesis of the polysaccharide backbone. Each species appears to employ a unique subset of modification enzymes for MGCx synthesis, likely accounting for the observed side chain diversity. Our results argue for the conservation of matrix function among spp. While biogenesis is preserved at the level of the mannan-glucan complex backbone, divergence emerges for construction of branching side chains. Thus, the MGCx backbone represents an ideal drug target for effective pan- species biofilm therapy. species, the most common fungal pathogens, frequently grow as a biofilm. These adherent communities tolerate extremely high concentrations of antifungal agents, due in large part, to a protective extracellular matrix. The present studies define the structural, functional, and genetic similarities and differences in the biofilm matrix from the four most common species. Each species synthesizes an extracellular mannan-glucan complex (MGCx) which contributes to sequestration of antifungal drug, shielding the fungus from this external assault. Synthesis of a common polysaccharide backbone appears conserved. However, subtle structural differences in the branching side chains likely rely upon unique modification enzymes, which are species specific. Our findings identify MGCx backbone synthesis as a potential pan- biofilm therapeutic target.
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http://dx.doi.org/10.1128/mBio.00451-18 | DOI Listing |
FEMS Microbiol Rev
November 2023
Department of Medicine, University of Wisconsin-Madison, 1685 Highland Ave Madison WI 53705, Madison.
Clinical infection due to Candida species frequently involve growth in biofilm communities. Recalcitrance despite antifungal therapy leads to disease persistence associated with high morbidity and mortality. Candida possesses several tools allowing evasion of antifungal effects.
View Article and Find Full Text PDFmBio
April 2018
Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA
biofilms resist the effects of available antifungal therapies. Prior studies with biofilms show that an extracellular matrix mannan-glucan complex (MGCx) contributes to antifungal sequestration, leading to drug resistance. Here we implement biochemical, pharmacological, and genetic approaches to explore a similar mechanism of resistance for the three most common clinically encountered non- species (NAC).
View Article and Find Full Text PDFVirulence of Candida is linked with its ability to form biofilms. Once established, biofilm infections are nearly impossible to eradicate. Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized.
View Article and Find Full Text PDFMol Cell Proteomics
December 2002
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
The cell wall proteins of Candida albicans play a key role in morphogenesis and pathogenesis and might be potential target sites for new specific antifungal drugs. However, these proteins are difficult to analyze because of their high heterogeneity, interconnections with wall polysaccharides (mannan, glucan, and chitin), low abundance, low solubility, and hydrophobic nature. Here we report a subproteomic approach for the study of the cell wall proteins (CWPs) from C.
View Article and Find Full Text PDFConventional techniques of chemical analysis have shown that the cell walls of the yeast Pichia polymorpha, at early stationary growth phase, consisted of carbohydrate (about 85%), protein (8%), and lipid (7%). Glucose and mannose were the only neutral sugars and glucosamine the sole amino sugar present among the cell wall components. Paper and gas-liquid chromatographies of acid hydrolysates of purified cell walls and cell wall fractions proved that mannan and alkali-insoluble glucans, in that order, were the major polysaccharide components, accounting for 83% of the total carbohydrate content.
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