title: Connexin 26 facilitates gastrointestinal bacterial infection in vitro.
abstract: Escherichia coli, including enteropathogenic E. coli (EPEC), represents the most common cause of diarrhoea worldwide and is therefore a serious public health burden. Treatment for gastrointestinal pathogens is hindered by the emergence of multiple antibiotic resistance, leading to the requirement for the development of new therapies. A variety of mechanisms act in combination to mediate gastrointestinal-bacterial-associated diarrhoea development. For example, EPEC infection of enterocytes induces attaching and effacing lesion formation and the disruption of tight junctions. An alternative enteric pathogen, Shigella flexneri, manipulates the expression of Connexin 26 (Cx26), a gap junction protein. S. flexneri can open Cx26 hemichannels allowing the release of ATP, whereas HeLa cells expressing mutant gap-junction-associated Cx26 are less susceptible to cellular invasion by S. flexneri than cells expressing wild-type (WT) Cx26. We have investigated further the link between Cx26 expression and gastrointestinal infection by using EPEC and S. flexneri as in vitro models of infection. In this study, a significant reduction in EPEC adherence was observed in cells expressing mutant Cx26 compared with WT Cx26. Furthermore, a significant reduction in both cellular invasion by S. flexneri and adherence by EPEC was demonstrated in human intestinal cell lines following treatment with Cx26 short interfering RNA. These in vitro results suggest that the loss of functional Cx26 expression provides improved protection against gastrointestinal bacterial pathogens. Thus, Cx26 represents a potential therapeutic target for gastrointestinal bacterial infection.
authors.affiliation: The Blizard Institute, Barts & The London School of Medicine and Dentistry, Queen Mary, University of London, London, UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Simpson
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsell
authors.forename: Olivier
authors.initials: O
authors.lastname: Marchès
mesh_terms: D001422:Bacterial Adhesion; D045744:Cell Line, Tumor; D000072259:Connexin 26; D017630:Connexins / Q000378:metabolism*; D004405:Dysentery, Bacillary / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D054308:Enteropathogenic Escherichia coli / Q000502:physiology*; D004927:Escherichia coli Infections / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005767:Gastrointestinal Diseases / Q000382:microbiology* / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D034741:RNA, Small Interfering / Q000378:metabolism; D012763:Shigella flexneri / Q000502:physiology*; D014162:Transfection
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D034741:RNA, Small Interfering; D000072259:Connexin 26; D049452:Green Fluorescent Proteins