Candida parapsilosis Protects Premature Intestinal Epithelial Cells from Invasion and Damage by Candida albicans

Abstract

Candida is a leading cause of late-onset sepsis in premature infants and is thought to invade the host via immature or damaged epithelial barriers. We previously showed that the hyphal form of Candida albicans invades and causes damage to premature intestinal epithelial cells (pIECs), whereas the non-hyphal Candida parapsilosis, also a fungal pathogen of neonates, has less invasion and damage abilities. In this study, we investigated the potential for C. parapsilosis to modulate pathogenic interactions of C. albicans with the premature intestine. While a mixed infection with two fungal pathogens may be expected to result in additive or synergistic damage to pIECs, we instead found that C. parapsilosis was able to protect pIECs from invasion and damage by C. albicans. C. albicans-induced pIEC damage was reduced to a similar extent by multiple different C. parapsilosis strains, but strains differed in their ability to inhibit C. albicans invasion of pIECs, with the inhibitory activity correlating with their adhesiveness for C. albicans and epithelial cells. C. parapsilosis cell-free culture fractions were also able to significantly reduce C. albicans adhesion and damage to pIECs. Furthermore, coadministration of C. parapsilosis cell-free fractions with C. albicans was associated with decreased infection and mortality in zebrafish. These results indicate that C. parapsilosis is able to reduce invasion, damage, and virulence functions of C. albicans. Additionally, the results with cellular and cell-free fractions of yeast cultures suggest that inhibition of pathogenic interactions between C. albicans and host cells by C. parapsilosis occurs via secreted molecules as well as by physical contact with the C. parapsilosis cell surface. We propose that non-invasive commensals can be used to inhibit virulence features of pathogens and deserve further study as a non-pharmacological strategy to protect the fragile epithelial barriers of premature infants.

The Zebrafish as a Model Host for Invasive Fungal Infections

“…Interestingly, C. parapsilosis tends to provoke little to no immune response to epithelial cells and can even block responses to C. albicans . Consistent results were found in both an in vitro epithelial- Candida challenge model and in the zebrafish swimbladder mucosal disease model, suggesting that secreted products from C. parapsilosis block epithelial immune responses to C. albicans [112]. When host responses to C. albicans and C. parapsilosis were compared in the swimbladder mucosal infection model, C. albicans activated the NF-κB pathway, evoked pro-inflammatory cytokines, and caused the recruitment of phagocytic immune cells while C. parapsilosis remained in yeast morphology and caused recruitment of phagocytes without inducing inflammation.…”

Intravital Imaging Reveals Divergent Cytokine and Cellular Immune Responses to Candida albicans and Candida parapsilosis

“…albicans and on virulence in swimbladder infection; this may explain the lack of immune signaling in response to C. parapsilosis in vivo seen here (97). Our results are consistent with the idea that epithelial cells have a prominent role in regulating the overall inflammatory response to Candida at mucosal surfaces, in addition to acting as a physical barrier and initiating immune responses (98–101).…”

Inhibitory Effect of Morin Against Candida albicans Pathogenicity and Virulence Factor Production: An in vitro and in vivo Approaches

“…As expected, the absence of these lesions in the treated group indicated the rescue action of morin treatment against C. albicans infection. Subsequently, the gross abnormalities, such as focal necrosis of tunica mucosa and lamina propria, severe EGCs infiltration, ulceration of the intestinal villi, and hyperplasia of the goblet cells, are denoted in the intestinal candidiasis in the infected group (Gonia et al, 2017), which are also oberved in C. albicans infected test organs' histopathology images. The disgusting abnormalities of congested distal tubulus, focal tubular necrosis, collapsed hemopoietic elements, and also the Bowman's space, is associated with the UTI-related pathogenic effect in the kidney of infected group (Rodríguez et al, 2009;Chang et al, 2016).…”