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Ca²⁺ release from host intracellular stores and related signal transduction during Campylobacter jejuni 81-176 internalization into human intestinal cells

¹ Laboratory of Enteric and Sexually Transmitted Diseases, FDA-Center for Biologics Evaluation and Research, 29 Lincoln Drive, Bldg 29/420 HFM440, Bethesda, MD 20892, USA
² Virulence Assessment, FDA-Center for Food Safety and Nutrition, Laurel, MD 20708, USA

Correspondence
Dennis J. Kopecko
kopecko{at}cber.fda.gov

Campylobacter jejuni is the leading bacterial cause of human diarrhoeal disease in many parts of the world, including the USA. The ability of C. jejuni to invade the host intestinal epithelium is an important determinant of virulence. A common theme among pathogenic invasive micro-organisms is their ability to usurp the eukaryotic cell-signalling systems both to allow for invasion and to trigger disease pathogenesis. Ca²⁺ is very important in a great variety of eukaryotic cell-signalling processes (e.g. calmodulin-activated enzymes, nuclear transcriptional upregulation, and cytoskeletal rearrangements). This study analyses the effects of Ca²⁺ availability on invasion of human INT407 intestinal epithelial cells by C. jejuni strain 81-176. The ability of C. jejuni to invade INT407 cells was not blocked by chelation of any remaining extracellular Ca²⁺ from host cells incubated in Ca²⁺-free, serum-free media. In contrast, C. jejuni invasion was markedly reduced either by chelating host intracellular Ca²⁺ with 1,2-bis-(2-)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA, AM) or by blocking the release of Ca²⁺ from intracellular stores with dantrolene or U73122. Moreover, Bay K8644, a plasma-membrane Ca²⁺-channel agonist, was observed to stimulate C. jejuni invasion, presumably by increasing host intracellular free Ca²⁺ levels. Measurement of host-cell cytosolic Ca²⁺ via spectrofluorimetry and fluorescence microscopy revealed an increase in Ca²⁺ from 10 min post-infection. Monolayer pretreatment with either a calmodulin antagonist or a specific inhibitor of protein kinase C was found to cause a marked reduction in C. jejuni invasion, suggesting roles for these Ca²⁺-activated modulators in signal-transduction events involved in C. jejuni invasion. These results demonstrate that C. jejuni induces the mobilization of Ca²⁺ from host intracellular stores, which is an essential step in the invasion of intestinal cells by this pathogen.

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				L. Hu, B. D. Tall, S. K. Curtis, and D. J. Kopecko Enhanced Microscopic Definition of Campylobacter jejuni 81-176 Adherence to, Invasion of, Translocation across, and Exocytosis from Polarized Human Intestinal Caco-2 Cells Infect. Immun., November 1, 2008; 76(11): 5294 - 5304. [Abstract] [Full Text] [PDF]