Candida albicans causes a diverse array of mucosal disease including oral and esophageal candidiasis and denture stomatitis. Reversible switching between several morphological forms seems to be crucial for virulence. Budding yeast are thought to aid dispersion across mucosal membranes, while the highly polarized hyphal form is suited to penetration and invasion of host tissue. The switch from yeast to hyphal growth is accompanied by a dramatic increase in vacuolar volume within the sub-apical compartments, making them look ‘empty'. We hypothesized this increase in vacuolar volume may increase turgor pressure within
C. albicans hyphae, enabling them to exert an ‘invasive force' on host tissue.
Objectives: 1. Determine if hyphal cell vacuolation coincides with increased turgor pressure; 2. Determine if vacuolation generates an ‘invasive force'; 3. Determine if vacuolar function is required for invasion of host tissue.
Methods: We identified
C. albicans proteins required for vacuole biogenesis. Mutant strains lacking these components were constructed. Invasion of nutrient plates with increasing agar content (to offer substrate resistance) was used to assess ‘invasive potential' of wild-type and mutant strains. A mouse model of candidiasis was used to test virulence and tissue invasion.
Results: Mutants lacking a vacuole have reduced filamentous growth. Also the mutant strains were less virulent than the wild-type control strain. Loss of virulence correlated with an inability to penetrate and invade host tissues.
Conclusion: Vacuolar expansion observed during
C. albicans filamentous outgrowth to generate ‘empty' hyphal compartments is required for hyphal growth, which is known to be required for pathogenicity. The avirulence of the vacuolar mutants seems to be due to an inability to invade or penetrate host tissues.
Supported by NCRR #P20RR020160.