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Antimicrobial Agents and Chemotherapy, December 2002, p. 3883-3891, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3883-3891.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Synthetic Peptides That Exert Antimicrobial Activities in Whole Blood and Blood-Derived Matrices

Michael R. Yeaman,1,2,3* Kimberly D. Gank,2 Arnold S. Bayer,1,2,3 and Eric P. Brass2,3,4

Department of Medicine, Division of Infectious Diseases,1 Center for Clinical Pharmacology, Harbor-UCLA Medical Center,4 Research and Education Institute at Harbor-UCLA, Torrance, California 90502,2 Department of Medicine, UCLA School of Medicine, Los Angeles, California 900253

Received 18 April 2002/ Returned for modification 18 June 2002/ Accepted 12 September 2002

Peptides that exert antimicrobial activity in artificial media may lack activity within blood or other complex biological matrices. To facilitate the evaluation of antimicrobial peptides for possible therapeutic utility, an ex vivo assay was developed to assess the extent and durability of peptide antimicrobial activities in complex fluid biomatrices of whole blood, plasma, and serum compared with those in conventional media. Novel antimicrobial peptides (RP-1 and RP-11) were designed based in part on platelet microbicidal proteins. RP-1, RP-11, or gentamicin was introduced into biomatrices either coincident with, or 2 h prior to, inoculation with an Escherichia coli target organism. Antimicrobial activities of peptides were assessed by quantitative culture 2 h after bacterial inoculation and compared to those of peptide-free and gentamicin controls. In whole blood and homologous plasma or serum, introduction of RP-1 or RP-11 coincident with E. coli was associated with a significant reduction in CFU per milliliter versus the respective peptide-free controls. Moreover, substantial antimicrobial activity remained when RP-1 or RP-11 was placed into whole blood or plasma 2 h prior to E. coli inoculation. These results suggest that the peptides were not rapidly inactivated within these biomatrices. Peptide antimicrobial activities were negatively affected by preincubation in serum or in heat-inactivated serum, compared with those of the respective controls. Peptides RP-1 and RP-11 were consistently effective at lower concentrations in biomatrices than in artificial media, indicating favorable antimicrobial interactions with components of blood or blood fractions. Collectively, these findings support the concept that synthetic peptides can be designed to exert potent antimicrobial activities in relevant and complex biological matrices.

* Corresponding author. Mailing address: Division of Infectious Diseases, Harbor-UCLA Medical Center, St. John's Cardiovascular Research Center, Harbor-UCLA Research and Education Institute, 1124 West Carson St., Torrance, CA 90502. Phone: (310) 222-6428. Fax: (310) 782-2016. E-mail: mryeaman{at}ucla.edu .

Antimicrobial Agents and Chemotherapy, December 2002, p. 3883-3891, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3883-3891.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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