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

Abstract

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