title: Mucin2 is Required for Probiotic Agents-Mediated Blocking Effects on Meningitic E. coli-Induced Pathogenicities.
abstract: Mucin2 (MUC2), an important regulatory factor in the immune system, plays an important role in the host defense system against bacterial translocation. Probiotics known to regulate MUC2 gene expression have been widely studied, but the interactions among probiotic, pathogens, and mucin gene are still not fully understood. The aim of this study was to investigate the role of MUC2 in blocking effects of probiotics on meningitic E. coli-induced pathogenicities. In this study, live combined probiotic tablets containing living Bifidobacterium, Lactobacillus bulgaricus, and Streptococcus thermophilus were used. MUC2 expression was knocked down in Caco-2 cells by RNA interference. 5-Aza-2'-deoxycytidine (5-Aza-CdR), which enhances mucin-promoted probiotic effects through inducing production of Sadenosyl- L-methionine (SAMe), was used to up-regulate MUC2 expression in Caco-2 cells. The adhesion to and invasion of meningitic E. coli were detected by competition assays. Our studies showed that probiotic agents could block E. coli-caused intestinal colonization, bacteremia, and meningitis in a neonatal sepsis and meningitis rat model. MUC2 gene expression in the neonatal rats given probiotic agents was obviously higher than that of the infected and uninfected control groups without probiotic treatment. The prohibitive effects of probiotic agents on MUC2-knockdown Caco-2 cells infected with E44 were significantly reduced compared with nontransfected Caco-2 cells. Moreover, the results also showed that 5- Aza-CdR, a drug enhancing the production of SAMe that is a protective agent of probiotics, was able to significantly suppress adhesion and invasion of E44 to Caco-2 cells by upregulation of MUC2 expression. Taken together, our data suggest that probiotic agents can efficiently block meningitic E. coli-induced pathogenicities in a manner dependent on MUC2.
authors.affiliation: Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.|Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA90027, USA.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Yu
authors.affiliation: Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: He
authors.affiliation: Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Santhosh
authors.initials: S
authors.lastname: Puthiyakunnon
authors.affiliation: Department of Clinic Laboratory, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, P.R. China.|The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Li-Sha
authors.initials: LS
authors.lastname: Wu
authors.affiliation: The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Peng
authors.affiliation: The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Yao-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Swapna
authors.initials: S
authors.lastname: Boddu
authors.affiliation: Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Long
authors.affiliation: Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.|Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA90027, USA.
authors.forename: Sheng-He
authors.initials: SH
authors.lastname: Huang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000898:Antibiosis; D001644:Bifidobacterium / Q000276:immunology* / Q000502:physiology; D018938:Caco-2 Cells; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000276:immunology* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000517:prevention & control; D006801:Humans; D007778:Lactobacillus / Q000276:immunology* / Q000502:physiology; D016920:Meningitis, Bacterial / Q000517:prevention & control; D008954:Models, Biological; D055262:Mucin-2 / Q000378:metabolism*; D019936:Probiotics / Q000494:pharmacology*; D051381:Rats; D018805:Sepsis / Q000517:prevention & control; D048249:Streptococcus thermophilus / Q000276:immunology* / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D055262:Mucin-2
keywords: Blood Brain Barrier; E. coli K1 (E44); MUC2; Probiotics agents; adhesion and invasion; neonatal sepsis and meningitis(NSM)