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Antimicrobial Agents and Chemotherapy, March 2009, p. 1210-1212, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.01294-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Efficient Neutralization of Antibody-Resistant Forms of Anthrax Toxin by a Soluble Receptor Decoy Inhibitor{triangledown}

Shilpi Sharma,1 Diane Thomas,2 John Marlett,1 Marianne Manchester,2 and John A. T. Young1*

The Salk Institute for Biological Studies, Infectious Disease Laboratory, 10010 North Torrey Pines Road, La Jolla, California 92037,1 Department of Cell Biology and Center for Integrative Molecular Biosciences, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 920372

Received 26 September 2008/ Returned for modification 18 November 2008/ Accepted 2 December 2008

A soluble receptor decoy inhibitor (RDI), comprised of the extracellular I domain of ANTXR2, is a candidate anthrax therapeutic. Here we show that RDI can effectively neutralize altered forms of the protective antigen toxin subunit that are resistant to 14B7 monoclonal antibody neutralization. These data highlight the potential of RDI to act as an adjunct to existing antibody-based therapies and indicate that inhibitors based on RDI might be useful as a stand-alone treatment against specifically engineered strains of Bacillus anthracis.

* Corresponding author. Mailing address: The Salk Institute for Biological Studies, Infectious Disease Laboratory, 10010 North Torrey Pines Road, La Jolla CA 92037. Phone: (858) 453-4100, ext. 1903. Fax: (858) 554-0341. E-mail: jyoung{at}salk.edu

{triangledown} Published ahead of print on 15 December 2008.

Antimicrobial Agents and Chemotherapy, March 2009, p. 1210-1212, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.01294-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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