title: Candida parapsilosisProtects Premature Intestinal Epithelial Cells from Invasion and Damage byCandida albicans.
abstract: Candidais a leading cause of late-onset sepsis in premature infants and is thought to invade the hostviaimmature or damaged epithelial barriers. We previously showed that the hyphal form ofCandida albicansinvades and causes damage to premature intestinal epithelial cells (pIECs), whereas the non-hyphalCandida parapsilosis, also a fungal pathogen of neonates, has less invasion and damage abilities. In this study, we investigated the potential forC. parapsilosisto modulate pathogenic interactions ofC. albicanswith 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 thatC. parapsilosiswas able to protect pIECs from invasion and damage byC. albicans.C. albicans-induced pIEC damage was reduced to a similar extent by multiple differentC. parapsilosisstrains, but strains differed in their ability to inhibitC. albicansinvasion of pIECs, with the inhibitory activity correlating with their adhesiveness forC. albicansand epithelial cells.C. parapsilosiscell-free culture fractions were also able to significantly reduceC. albicansadhesion and damage to pIECs. Furthermore, coadministration ofC. parapsilosiscell-free fractions withC. albicanswas associated with decreased infection and mortality in zebrafish. These results indicate thatC. parapsilosisis able to reduce invasion, damage, and virulence functions ofC. albicans. Additionally, the results with cellular and cell-free fractions of yeast cultures suggest that inhibition of pathogenic interactions betweenC. albicansand host cells byC. parapsilosisoccursviasecreted molecules as well as by physical contact with theC. parapsilosiscell 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.
authors.affiliation: Department of Pediatrics, University of Minnesota , Minneapolis, MN , USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Gonia
authors.affiliation: Department of Molecular and Biomedical Sciences, University of Maine , Orono, ME , USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Archambault
authors.affiliation: Department of Pediatrics, University of Minnesota , Minneapolis, MN , USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Shevik
authors.affiliation: Department of Pediatrics, University of Minnesota , Minneapolis, MN , USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Altendahl
authors.affiliation: Department of Pediatrics, University of Minnesota , Minneapolis, MN , USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Fellows
authors.affiliation: Department of Pediatrics, Women & Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University , Providence, RI , USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Bliss
authors.affiliation: Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME, USA; Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Wheeler
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Gale
keywords: Candida albicans; Candida parapsilosis; fungal pathogenesis; intestinal epithelium; premature infant; zebrafish model system