Global cell surface conformational shift mediated by a Candida albicans adhesin

Area of Science:

• Microbiology
• Cell Biology
• Biochemistry

Background:

• Candida albicans exists as both commensal and pathogenic organisms in humans.
• Cell surface adhesins, particularly the Als family, are crucial for both states.
• Als adhesins mediate interactions with various ligands and facilitate cell aggregation.

Purpose of the Study:

• To investigate the mechanism of Als5p-mediated cell-cell aggregation.
• To explore the role of protein conformation and cell surface properties in aggregation.

Main Methods:

• Heterologous expression of Als5p in Saccharomyces cerevisiae.
• Adhesion assays using fibronectin-coated beads.
• Analysis of aggregation in the presence of metabolic, signal transduction, and protein perturbants (ANS, Congo Red).
• Measurement of cell surface hydrophobicity via ANS fluorescence.
• Assessment of cell surface order using aggregation-induced birefringence.

Main Results:

• Als5p expression promoted adhesion and subsequent multicellular aggregate formation.
• Aggregation was inhibited by perturbants (ANS, Congo Red) that affect protein structure.
• Cell adhesion led to increased cell surface hydrophobicity and aggregation-induced birefringence.
• Inhibition of aggregation correlated with the disruption of these surface changes.

Conclusions:

• Als5p-mediated aggregation involves an adhesion-triggered conformational change.
• This conformational change propagates across the cell surface, creating ordered aggregation-competent regions.
• Cell surface hydrophobicity and structural order are key to C. albicans aggregation.