Candida albicans: The Ability to Invade Epithelial Cells and Survive under Oxidative Stress Is Unlinked to Hyphal Length

Abstract

In its hyphal form, Candida albicans invades epithelial and endothelial cells by two distinct mechanisms: active penetration and induced endocytosis. The latter is dependent on a reorganization of the host cytoskeleton (actin/cortactin recruitment), whilst active penetration does not rely on the host's cellular machinery. The first obstacle for the fungus to reach deep tissues is the epithelial barrier and this interaction is crucial for commensal growth, fungal pathogenicity and host defense. This study aimed to characterize in vitro epithelial HeLa cell invasion by four different isolates of C. albicans with distinct clinical backgrounds, including a C. albicans SC5314 reference strain. All isolates invaded HeLa cells, recruited actin and cortactin, and induced the phosphorylation of both Src-family kinases (SFK) and cortactin. Curiously, L3881 isolated from blood culture of a patient exhibited the highest resistance to oxidative stress, although this isolate showed reduced hyphal length and displayed the lowest cell damage and invasion rates. Collectively, these data suggest that the ability of C. albicans to invade HeLa cells, and to reach and adapt to the host's blood, including resistance to oxidative stress, may be independent of hyphal length.

Candida albicans—The Virulence Factors and Clinical Manifestations of Infection

“…The transition from yeast to the hyphal form is a transition into a pathogenic form [ 22 , 23 ]. The hyphal form is invasive, and in this form, the cells enter the host tissue by active penetration and induced endocytosis [ 24 ] ( Figure 2 ). Induced endocytosis is mediated by hyphae invasion and depends on host activity, whereas active penetration depends on the fungal activity [ 25 ].…”

Comparative molecular and immunoregulatory analysis of extracellular vesicles fromCandida albicansandCandida auris

“…Adhesion of yeast cells to epithelial surfaces is an important mechanism of disease as an initial step for further tissue damage and colonization of distinct sites in the host, including the bloodstream 52 . C. albicans can interact with surface adhesion molecules on epithelial cells 50,51 , so we investigated whether EVs from both Candida species were able to modulate the adhesion of yeast to epithelial monolayers in vitro. Although the tested strains were able to adhere to the epithelial monolayer, a significant increase in adhesion was observed when EVs from C. auris MMC1 were added to the monolayer.…”

“…Adhesion to epithelial surfaces is an important feature displayed by pathogenic species of Candida as an early stage of colonization of host tissues [49][50][51][52] . We evaluated whether The graph shows average and standard errors relative to 2 independent experiments.…”

MSS2 maintains mitochondrial function and is required for chitosan resistance, invasive growth, biofilm formation and virulence in Candida albicans

“…The experimental procedures of the cell invasive assays followed the established protocol with slight modifications [ 73 , 74 ]. Overnight cultures of HeLa cells on the glass coverslips were washed with PBS and incubated with 5 × 10 5 C. albicans cells at 37°C with 5% CO 2 for 1 hr.…”