Dataset Information

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).

SUBMITTER: Dean P

PROVIDER: S-EPMC4661573 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Cultured enterocytes internalise bacteria across their basolateral surface for, pathogen-inhibitable, trafficking to the apical compartment.

Dean Paul P Quitard Sabine S Bulmer David M DM Roe Andrew J AJ Kenny Brendan B

Scientific reports 20151127

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. Ant ...[more]

PMID: 26612456

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Project description:Pseudomonas aeruginosa, an important opportunistic pathogen of man, exploits numerous factors for initial attachment to the host, an event required to establish bacterial infection. In this paper, we rigorously explore the role of two major bacterial adhesins, type IV pili (Tfp) and flagella, in bacterial adherence to distinct host receptors at the apical (AP) and basolateral (BL) surfaces of polarized lung epithelial cells and induction of subsequent host signaling and pathogenic events. Using an isogenic mutant of P. aeruginosa that lacks flagella or utilizing beads coated with purified Tfp, we establish that Tfp are necessary and sufficient for maximal binding to host N-glycans at the AP surface of polarized epithelium. In contrast, experiments utilizing a P. aeruginosa isogenic mutant that lacks Tfp or using beads coated with purified flagella demonstrate that flagella are necessary and sufficient for maximal binding to heparan sulfate (HS) chains of heparan sulfate proteoglycans (HSPGs) at the BL surface of polarized epithelium. Using two different cell-free systems, we demonstrate that Tfp-coated beads show highest binding affinity to complex N-glycan chains coated onto plastic plates and preferentially aggregate with beads coated with N-glycans, but not with single sugars or HS. In contrast, flagella-coated beads bind to or aggregate preferentially with HS or HSPGs, but demonstrate little binding to N-glycans. We further show that Tfp-mediated binding to host N-glycans results in activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway and bacterial entry at the AP surface. At the BL surface, flagella-mediated binding to HS activates the epidermal growth factor receptor (EGFR), adaptor protein Shc, and PI3K/Akt, and induces bacterial entry. Remarkably, flagella-coated beads alone can activate EGFR and Shc. Together, this work provides new insights into the intricate interactions between P. aeruginosa and lung epithelium that may be potentially useful in the development of novel treatments for P. aeruginosa infections.

Dataset Information

Cultured enterocytes internalise bacteria across their basolateral surface for, pathogen-inhibitable, trafficking to the apical compartment.

Publications

Cultured enterocytes internalise bacteria across their basolateral surface for, pathogen-inhibitable, trafficking to the apical compartment.

Similar Datasets

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