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Infection and Immunity, June 2009, p. 2455-2464, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.00839-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Bacillus anthracis Edema Toxin Impairs Neutrophil Actin-Based Motility{triangledown}

Sarah E. Szarowicz,1 Russell L. During,1 Wei Li,1 Conrad P. Quinn,2 Wei-Jen Tang,3 and Frederick S. Southwick1*

Division of Infectious Diseases, College of Medicine, University of Florida, Gainesville, Florida 32610,1 NCIRD, DBD, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,2 Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 606373

Received 7 July 2008/ Returned for modification 8 July 2008/ Accepted 26 March 2009

Inhalation anthrax results in high-grade bacteremia and is accompanied by a delay in the rise of the peripheral polymorphonuclear neutrophil (PMN) count and a paucity of PMNs in the infected pleural fluid and mediastinum. Edema toxin (ET) is one of the major Bacillus anthracis virulence factors and consists of the adenylate cyclase edema factor (EF) and protective antigen (PA). Relatively low concentrations of ET (100 to 500 ng/ml of PA and EF) significantly impair human PMN chemokinesis, chemotaxis, and ability to polarize. These changes are accompanied by a reduction in chemoattractant-stimulated PMN actin assembly. ET also causes a significant decrease in Listeria monocytogenes intracellular actin-based motility within HeLa cells. These defects in actin assembly are accompanied by a >50-fold increase in intracellular cyclic AMP and a >4-fold increase in the phosphorylation of protein kinase A. We have previously shown that anthrax lethal toxin (LT) also impairs neutrophil actin-based motility (R. L. During, W. Li, B. Hao, J. M. Koenig, D. S. Stephens, C. P. Quinn, and F. S. Southwick, J. Infect. Dis. 192:837-845, 2005), and we now find that LT combined with ET causes an additive inhibition of PMN chemokinesis, polarization, chemotaxis, and FMLP (N-formyl-met-leu-phe)-induced actin assembly. We conclude that ET alone or combined with LT impairs PMN actin assembly, resulting in paralysis of PMN chemotaxis.

* Corresponding author. Mailing address: Division of Infectious Diseases, Box 100277, University of Florida College of Medicine, Gainesville, FL 32610. Phone: (352) 392-4058. Fax: (352) 392-6481. E-mail: Southfs{at}medicine.ufl.edu

{triangledown} Published ahead of print on 6 April 2009.

Editor: S. R. Blanke

Infection and Immunity, June 2009, p. 2455-2464, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.00839-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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