Sara Gonia1, Michele Tuepker1, Timothy Heisel1, Chloe Autran2, Lars Bode2, Cheryl A Gale3. 1. Departments of Pediatrics and. 2. Department of Pediatrics, University of California, San Diego, La Jolla, CA. 3. Departments of Pediatrics and Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN; and galex012@umn.edu.
Abstract
BACKGROUND: Human milk oligosaccharides (HMOs) are a highly abundant, diverse group of unique glycans that are postulated to promote the development of a protective bacterial microbiota in the intestine and prevent adhesive and invasive interactions of pathogenic bacteria with mucosal epithelia. Candida albicans, a prevalent fungal colonizer of the neonatal gut, causes the majority of fungal disease in premature infants and is highly associated with life-threatening intestinal disorders. OBJECTIVE: The objective of the current study was to test the hypothesis that HMOs protect human premature intestinal epithelial cells (pIECs) from invasion by C. albicans. METHODS: To study fungal invasion, a quantitative immunocytochemical assay was used to distinguish invading from noninvading C. albicans cells in the presence and absence of HMOs. To understand how HMOs affect C. albicans invasion of pIECs, the expression of C. albicans virulence traits that are important for invasiveness (hyphal morphogenesis and ability to associate with host cells) were quantified. RESULTS: Treatment with HMOs reduced invasion of pIECs by C. albicans in a dose-dependent manner by 14-67%, with a physiologic concentration (15mg/mL) of HMOs causing a 52% reduction in invasion (P < 0.05). The decreased invasive ability of C. albicans was associated with hyphal lengths that were ∼30% shorter (P < 0.05), likely because of a delay in the induction of hyphal morphogenesis after inoculation of yeast onto pIECs, which correlated with a 23% reduction in the combined expression level of hyphal-specific genes (P < 0.05). In addition, HMOs caused a 40% decrease in the number of C. albicans cells able to associate with pIECs at the time of hyphal induction (P < 0.05). CONCLUSIONS: These results, obtained with the use of a primary pIEC model, indicate that HMOs reduce virulence characteristics of C. albicans and suggest a role for HMOs in protecting the premature infant intestine from invasion and damage by C. albicans hyphae.
BACKGROUND:Human milk oligosaccharides (HMOs) are a highly abundant, diverse group of unique glycans that are postulated to promote the development of a protective bacterial microbiota in the intestine and prevent adhesive and invasive interactions of pathogenic bacteria with mucosal epithelia. Candida albicans, a prevalent fungal colonizer of the neonatal gut, causes the majority of fungal disease in premature infants and is highly associated with life-threatening intestinal disorders. OBJECTIVE: The objective of the current study was to test the hypothesis that HMOs protect human premature intestinal epithelial cells (pIECs) from invasion by C. albicans. METHODS: To study fungal invasion, a quantitative immunocytochemical assay was used to distinguish invading from noninvading C. albicans cells in the presence and absence of HMOs. To understand how HMOs affect C. albicans invasion of pIECs, the expression of C. albicans virulence traits that are important for invasiveness (hyphal morphogenesis and ability to associate with host cells) were quantified. RESULTS: Treatment with HMOs reduced invasion of pIECs by C. albicans in a dose-dependent manner by 14-67%, with a physiologic concentration (15mg/mL) of HMOs causing a 52% reduction in invasion (P < 0.05). The decreased invasive ability of C. albicans was associated with hyphal lengths that were ∼30% shorter (P < 0.05), likely because of a delay in the induction of hyphal morphogenesis after inoculation of yeast onto pIECs, which correlated with a 23% reduction in the combined expression level of hyphal-specific genes (P < 0.05). In addition, HMOs caused a 40% decrease in the number of C. albicans cells able to associate with pIECs at the time of hyphal induction (P < 0.05). CONCLUSIONS: These results, obtained with the use of a primary pIEC model, indicate that HMOs reduce virulence characteristics of C. albicans and suggest a role for HMOs in protecting the premature infant intestine from invasion and damage by C. albicans hyphae.
Authors: Christian Milani; Sabrina Duranti; Francesca Bottacini; Eoghan Casey; Francesca Turroni; Jennifer Mahony; Clara Belzer; Susana Delgado Palacio; Silvia Arboleya Montes; Leonardo Mancabelli; Gabriele Andrea Lugli; Juan Miguel Rodriguez; Lars Bode; Willem de Vos; Miguel Gueimonde; Abelardo Margolles; Douwe van Sinderen; Marco Ventura Journal: Microbiol Mol Biol Rev Date: 2017-11-08 Impact factor: 11.056