Anthrax edema toxin inhibits Nox1-mediated formation of reactive oxygen species by colon epithelial cells.
One major route of intoxication by Bacillus anthracis (anthrax) spores is via their ingestion and subsequent uptake by the intestinal epithelium. Anthrax edema toxin (ETx) is an adenylate cyclase that causes persistent elevation of cAMP in intoxicated cells. NADPH oxidase enzymes (Nox1-Nox5, Duox1 and 2) generate reactive oxygen species (ROS) as components of the host innate immune response to bacteria, including Nox1 in gastrointestinal epithelial tissues. We show that ETx effectively inhibits ROS formation by Nox1 in HT-29 colon epithelial cells. This inhibition requires the PKA-mediated phosphorylation of the Nox1-regulatory component, NoxA1, and the subsequent binding of 14-3-3zeta. Inhibition of Nox1-mediated ROS formation in the gut epithelium may be a mechanism used by B. anthracis to circumvent the innate immune response.
Kim
Jun-Sub
JS
Department of Immunology, Scripps Research Institute, La Jolla, Calif., USA.
Bokoch
Gary M
GM
D000881:Anthrax / Q000276:immunology*; D000942:Antigens, Bacterial / Q000378:metabolism*; D001408:Bacillus anthracis / Q000201:enzymology*; D001427:Bacterial Toxins / Q000378:metabolism*; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism* / Q000382:microbiology; D015536:Down-Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D017382:Reactive Oxygen Species; C030325:anthrax toxin; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human