title: Targeting and alteration of tight junctions by bacteria and their virulence factors such as Clostridium perfringens enterotoxin.
abstract: The integrity of tight junctions, which regulate paracellular permeability, is challenged by many bacterial pathogens. This is caused by inflammatory responses triggered by pathogens and direct interaction of bacteria or their toxins with host epithelial cells. In some cases, tight junction proteins represent receptors for cell surface proteins or toxins of the pathogen, such as Clostridium perfringens enterotoxin (CPE). CPE causes diarrhea and cramps-the symptoms of a common foodborne illness, caused by C. perfringens type A. It uses a subgroup of the claudin family of tight junction proteins as receptors and forms pores in the membrane of intestinal epithelial cells. Ca2+influx through these pores finally triggers cell damage. In this review, we summarize tight junction targeting and alteration by a multitude of different microorganisms such as C. perfringens, Escherichia coli, Helicobacter pylori, Salmonella typhimurium, Shigella flexneri, Vibrio cholerae, Yersinia enterocolitica, protozoan parasites, and their proteins. A focus is drawn towards CPE, the interaction with its receptors, cellular, and pathophysiological consequences for the intestinal epithelium. In addition, we portend to the use of CPE-based claudin modulators for drug delivery as well as diagnosis and therapy of cancer.
authors.affiliation: Institute of Clinical Physiology, Charité-Universitätsmedizin Berlin, 12203, Berlin, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Eichner
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), 13125, Berlin, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Protze
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), 13125, Berlin, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Piontek
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), 13125, Berlin, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Krause
authors.affiliation: Institute of Clinical Physiology, Charité-Universitätsmedizin Berlin, 12203, Berlin, Germany. joerg.piontek@charite.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Piontek
mesh_terms: D000818:Animals; D003016:Clostridium perfringens / Q000378:metabolism*; D004768:Enterotoxins / Q000378:metabolism*; D006801:Humans; D062725:Tight Junction Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism* / Q000382:microbiology*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D004768:Enterotoxins; D062725:Tight Junction Proteins; D037521:Virulence Factors; C035598:enterotoxin, Clostridium
keywords: Bacterial receptors; Claudin targeting; Clostridium perfringens enterotoxin; Intestinal barrier; Pore-forming toxin