Trans-cellular tunnels induced by the fungal pathogen Candida albicans facilitate invasion through successive epithelial cells without host damage

Abstract

The opportunistic fungal pathogen Candida albicans is normally commensal, residing in the mucosa of most healthy individuals. In susceptible hosts, its filamentous hyphal form can invade epithelial layers leading to superficial or severe systemic infection. Invasion is mainly intracellular, though it causes no apparent damage to host cells. We investigated the invasive lifestyle of Candida albicansin vitro using live-cell imaging and the damage-sensitive reporter galectin-3. Quantitative single cell analysis showed that invasion can result in host membrane breaching at different stages of invasion and cell death, or in traversal of host cells without membrane breaching. Membrane labelling and three-dimensional volume electron microscopy revealed that hyphae can traverse several host cells within trans-cellular tunnels that are progressively remodelled and may undergo inflations linked to host glycogen stores, possibly during nutrient uptake. Thus, Candida albicans invade epithelial tissues by either inflicting or avoiding host damage, the latter facilitated by trans-cellular tunnelling.

Calcium-dependent ESCRT recruitment and lysosome exocytosis maintain epithelial integrity during Candida albicans invasion

“…We found that the host implements robust responses to offset the stresses C. albicans creates on the epithelial PM during invasion. By electron microscopy, the invasion pocket was reported recently to have inflated membranes with numerous associated vesicles ( Lechat, 2021 ), reminiscent of the blebs we document. Our cell-based studies are also in accordance with in vivo mouse and zebrafish candidiasis models that link ECE1 expression with C. albicans pathogenicity and invasiveness ( Moyes et al., 2010 ; Swidergall et al., 2019 ).…”