Candida albicans-Epithelial Interactions: Dissecting the Roles of Active Penetration, Induced Endocytosis and Host Factors on the Infection Process

Abstract

Candida albicans frequently causes superficial infections by invading and damaging epithelial cells, but may also cause systemic infections by penetrating through epithelial barriers. C. albicans is a remarkable pathogen because it can invade epithelial cells via two distinct mechanisms: induced endocytosis, analogous to facultative intracellular enteropathogenic bacteria, and active penetration, similar to plant pathogenic fungi. Here we investigated the contributions of the two invasion routes of C. albicans to epithelial invasion. Using selective cellular inhibition approaches and differential fluorescence microscopy, we demonstrate that induced endocytosis contributes considerably to the early time points of invasion, while active penetration represents the dominant epithelial invasion route. Although induced endocytosis depends mainly on Als3-E–cadherin interactions, we observed E–cadherin independent induced endocytosis. Finally, we provide evidence of a protective role for serum factors in oral infection: human serum strongly inhibited C. albicans adhesion to, invasion and damage of oral epithelial cells.

Candidiasis: Predisposing Factors, Prevention, Diagnosis and Alternative Treatment

“…There are several classes of candidiasis, which have become more common in recent years [4,6,13,17,40,41].…”

“…Although this yeast is responsible for approximately 50-90% of human candidiasis, C. albicans is part of the commensal flora of more than half of the healthy population. Colonization by this yeast is beneficial to the host, because not only limits the growth of other opportunistic pathogenic fungi, but also promotes the functioning of the immune system [1][2][3][4][5].…”

“…In the last two decades, it has been observed a considerable increase in the incidence of deep fungal infections, not only in immunocompromised patients, but also related to nosocomial infections, and even in healthy population [4,[6][7][8][9][10][11][12][13][14][15]. Thus, with the increased incidence of deep fungal infections (chronic candidiasis), the primitive idea that they were related to a restrict number of pathogenic fungi and specific geographical area was completely changed.…”

Host Cell Invasion by Medically Important Fungi

“…albicans can invade epithelial cells by two different mechanisms: induced endocytosis and active penetration (Park et al 2005;Zakikhany et al 2007;Dalle et al 2010;Zhu and Filler 2010;Wachtler et al 2012). In addition, C. albicans can invade epithelial cell barriers by a paracellular route that involves the proteolytic digestion of tight junctions (Frank and Hostetter 2007;Villar et al 2007;Rollenhagen et al 2009).…”

“…This defect in two different host cell invasion mechanisms is the likely explanation for the profound virulence attenuation of the hyphal-deficient C. albicans mutant that lacks the Efg1 transcription factor (Park et al 2005). On the other hand, although the als3D/D mutant forms normal length hyphae, it is defective in both induced endocytosis and active penetration in vitro (Phan et al 2007;Wachtler et al 2012). It is postulated that Als3 is required for active penetration because it helps anchor the C. albicans cell to the epithelial cell.…”