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Antimicrobial Agents and Chemotherapy, June 2006, p. 2132-2136, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00120-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Antibody-Guided Alpha Radiation Effectively Damages Fungal Biofilms

L. R. Martinez,¹ R. A. Bryan,² C. Apostolidis,³ A. Morgenstern,³ A. Casadevall,^1,4, and E. Dadachova^1,2*,

Departments of Microbiology and Immunology,¹ Nuclear Medicine,² Medicine, Albert Einstein College of Medicine, Bronx, New York,⁴ European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany³

Received 29 January 2006/ Returned for modification 17 March 2006/ Accepted 26 March 2006

The use of indwelling medical devices—pacemakers, prosthetic joints, catheters—is rapidly growing and is often complicated by infections with biofilm-forming microbes that are resistant to antimicrobial agents and host defense mechanisms. We investigated for the first time the use of microbe-specific monoclonal antibodies (MAbs) as delivery vehicles for targeting biofilms with cytocidal radiation. MAb 18B7 (immunoglobulin G1 [IgG1]), which binds to capsular polysaccharides of the human pathogenic fungus Cryptococcus neoformans, penetrated cryptococcal biofilms, as shown by confocal microscopy. When the alpha radiation-emitter 213-Bismuth (²¹³Bi) was attached to MAb 18B7 and the radiolabeled MAb was added to C. neoformans biofilms, there was a 50% reduction in biofilm metabolic activity. In contrast, when the IgM MAb 13F1 labeled with ²¹³Bi was used there was no penetration of the fungal biofilm and no damage. Unlabeled 18B7, ²¹³Bi-labeled nonspecific MAbs, and gamma and beta types of radiation did not have an effect on biofilms. The lack of efficacy of gamma and beta radiation probably reflects the radioprotective properties of polysaccharide biofilm matrix. Our results indicate that C. neoformans biofilms are susceptible to treatment with antibody-targeted alpha radiation, suggesting a novel option for the prevention or treatment of microbial biofilms on indwelling medical devices.

E. D. and A. C. share senior authorship of the paper.

This article has been cited by other articles:

• Bryan, R. A., Huang, X., Morgenstern, A., Bruchertseifer, F., Casadevall, A., Dadachova, E. (2008). Radiofungicidal Effects of External Gamma Radiation and Antibody-Targeted Beta and Alpha Radiation on Cryptococcus neoformans. Antimicrob. Agents Chemother. 52: 2232-2235 [Abstract] [Full Text]