The cooperative action of bacterial fibronectin-binding proteins and secreted proteins promote maximal Campylobacter jejuni invasion of host cells by stimulating membrane ruffling

Tyson P Eucker; Michael E Konkel

doi:10.1111/j.1462-5822.2011.01714.x

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The cooperative action of bacterial fibronectin-binding proteins and secreted proteins promote maximal Campylobacter jejuni invasion of host cells by stimulating membrane ruffling

Journal article

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The cooperative action of bacterial fibronectin-binding proteins and secreted proteins promote maximal Campylobacter jejuni invasion of host cells by stimulating membrane ruffling

Tyson P Eucker and Michael E Konkel

Cellular microbiology, Vol.14(2), pp.226-238

02/2012

DOI: https://doi.org/10.1111/j.1462-5822.2011.01714.x

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https://hdl.handle.net/2376/109277

PMCID: PMC3262099

PMID: 21999233

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https://doi.org/10.1111/j.1462-5822.2011.01714.xView

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Abstract

Cell Line

Epithelial Cells - metabolism

Immunoprecipitation

Campylobacter jejuni - pathogenicity

Signal Transduction

Humans

Gene Silencing

Epidermal Growth Factor - metabolism

Immunoblotting

Gene Expression Profiling

Bacterial Adhesion

Host-Pathogen Interactions

Adhesins, Bacterial - metabolism

Models, Biological

Epithelial Cells - microbiology

Campylobacter jejuni - metabolism

Virulence Factors - metabolism

Cell Membrane - metabolism

Cell Membrane - microbiology

Microscopy, Fluorescence

This study was performed to elucidate the host cell scaffolding and signalling molecules that Campylobacter jejuni utilizes to invade epithelial cells. We hypothesized that the C. jejuni fibronectin-binding proteins and secreted proteins are required for cell signalling and maximal invasion of host cells. C. jejuni binding to host cells via the CadF and FlpA fibronectin-binding proteins activated the epidermal growth factor (EGF) pathway, as evidenced by inhibitor studies and immunoprecipitation coupled with immunoblot analysis using antibodies reactive against total and active EGF receptor. Inhibitor studies revealed maximal C. jejuni host cell invasion was dependent upon PI3-Kinase, c-Src and focal adhesion kinase (FAK), all of which are known to participate in cytoskeletal rearrangements. Knockdown of endogenous Dock180, which is a Rac1-specific guanine nucleotide exchange factor, using siRNA revealed that C. jejuni invasion was significantly reduced compared with cells treated with scrambled siRNA. We further demonstrated that the C. jejuni Cia proteins are, in part, responsible for Rho GTPase Rac1 recruitment and activation, as judged by immunofluorescence microscopy and Rac1 activation. Based on these data, we present a model that illustrates that C. jejuni utilizes a coordinated mechanism involving both adhesins and secreted proteins to promote membrane ruffling and host cell invasion.

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Title: The cooperative action of bacterial fibronectin-binding proteins and secreted proteins promote maximal Campylobacter jejuni invasion of host cells by stimulating membrane ruffling
Creators: Tyson P Eucker - School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7520, USA
Michael E Konkel
Publication Details: Cellular microbiology, Vol.14(2), pp.226-238
Academic Unit: Molecular Biosciences, School of
Publisher: England
Grant note: T32 GM008336 / NIGMS NIH HHS T32 GM008336-23 / NIGMS NIH HHS R56 AI088518 / NIAID NIH HHS R56 AI088518-01A1 / NIAID NIH HHS T32GM008336 / NIGMS NIH HHS
Identifiers: 99900547322601842
Language: English
Resource Type: Journal article