title: Cultured enterocytes internalise bacteria across their basolateral surface for, pathogen-inhibitable, trafficking to the apical compartment.
abstract: In vitro- and in vivo-polarised absorptive epithelia (enterocytes) are considered to be non-phagocytic towards bacteria with invasive pathogenic strains relying on virulence factors to 'force' entry. Here, we report a serendipitous discovery that questions these beliefs. Thus, we uncover in well-established models of human small (Caco-2; TC-7) and large (T84) intestinal enterocytes a polarization-dependent mechanism that can transfer millions of bacteria from the basal to apical compartment. Antibiotic-protection assays, confocal imaging and drug inhibitor data are consistent with a transcellular route in which internalized, basolateral-membrane enclosed bacteria are trafficked to and across the apical surface. Basal-to-apical transport of non-pathogenic bacteria (and inert beads) challenged the idea of pathogens relying on virulence factors to force entry. Indeed, studies with Salmonella demonstrated that it's entry-forcing virulence factor (SPI-I) was not required to enter via the basolateral surface but to promote another virulence-associated event (intra-enterocyte accumulation).
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Medical School, Newcastle-upon-Tyne, NE2 4HH, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Dean
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Medical School, Newcastle-upon-Tyne, NE2 4HH, United Kingdom.
authors.forename: Sabine
authors.initials: S
authors.lastname: Quitard
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Medical School, Newcastle-upon-Tyne, NE2 4HH, United Kingdom.
authors.forename: David M
authors.initials: DM
authors.lastname: Bulmer
authors.affiliation: Institute of Infection, Immunity and Immunology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Roe
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Medical School, Newcastle-upon-Tyne, NE2 4HH, United Kingdom.
authors.forename: Brendan
authors.initials: B
authors.lastname: Kenny
mesh_terms: D018988:Bacterial Translocation; D001692:Biological Transport; D018938:Caco-2 Cells; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology; D020895:Enterocytes / Q000187:drug effects / Q000382:microbiology*; D054308:Enteropathogenic Escherichia coli / Q000472:pathogenicity / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D012486:Salmonella typhimurium / Q000472:pathogenicity / Q000502:physiology; D037521:Virulence Factors / Q000494:pharmacology
chemical_list: D037521:Virulence Factors