title: Influence of adhesion and bacteriocin production by Lactobacillus salivarius on the intestinal epithelial cell transcriptional response.
abstract: Lactobacillus salivarius strain UCC118 is a human intestinal isolate that has been extensively studied for its potential probiotic effects in human and animal models. The objective of this study was to determine the effect of L. salivarius UCC118 on gene expression responses in the Caco-2 cell line to improve understanding of how the strain might modulate intestinal epithelial cell phenotypes. Exposure of Caco-2 cells to UCC118 led to the induction of several human genes (TNFAIP3, NFKBIA, and BIRC3) that are negative regulators of inflammatory signaling pathways. Induction of chemokines (CCL20, CXCL-1, and CXCL-2) with antimicrobial functions was also observed. Disruption of the UCC118 sortase gene srtA causes reduced bacterial adhesion to epithelial cells. Transcription of three mucin genes was reduced significantly when Caco-2 cells were stimulated with the ΔsrtA derivative of UCC118 compared to cells stimulated with the wild type, but there was no significant change in the transcription levels of the anti-inflammatory genes. UCC118 genes that were significantly upregulated upon exposure to Caco-2 cells were identified by bacterial genome microarray and consisted primarily of two groups of genes connected with purine metabolism and the operon for synthesis of the Abp118 bacteriocin. Following incubation with Caco-2 cells, the bacteriocin synthesis genes were transcribed at higher levels in the wild type than in the ΔsrtA derivative. These data indicate that L. salivarius UCC118 influences epithelial cells both through modulation of the inflammatory response and by modulation of intestinal cell mucin production. Sortase-anchored cell surface proteins of L. salivarius UCC118 have a central role in promoting the interaction between the bacterium and epithelial cells.
authors.affiliation: Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: O'Callaghan
authors.forename: Ludovica F
authors.initials: LF
authors.lastname: Buttó
authors.forename: John
authors.initials: J
authors.lastname: MacSharry
authors.forename: Kenneth
authors.initials: K
authors.lastname: Nally
authors.forename: Paul W
authors.initials: PW
authors.lastname: O'Toole
mesh_terms: D019881:Aminoacyltransferases / Q000378:metabolism; D000704:Analysis of Variance; D001422:Bacterial Adhesion / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism; D001430:Bacteriocins / Q000096:biosynthesis*; D018938:Caco-2 Cells; D018925:Chemokines / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D007778:Lactobacillus / Q000378:metabolism / Q000502:physiology*; D046228:Microarray Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D001430:Bacteriocins; D018925:Chemokines; D017931:DNA Primers; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases