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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.

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