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Antimicrobial Agents and Chemotherapy, October 2001, p. 2820-2825, Vol. 45, No. 10
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.10.2820-2825.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

High Therapeutic Index of Factor C Sushi Peptides: Potent Antimicrobials against Pseudomonas aeruginosa

Yin Hoe Yau,¹ Bow Ho,² Nguan Soon Tan, Miang Lon Ng,¹ and Jeak Ling Ding^1,*

Department of Biological Sciences¹ and Department of Microbiology,² National University of Singapore, Singapore 117543

Received 19 January 2001/Returned for modification 8 May 2001/Accepted 27 July 2001

Factor C protein isolated from the horseshoe crab, Carcinoscorpius rotundicauda, has endotoxin binding capability. Synthetic peptides of 34 amino acids based on the sequence of two regions of factor C (Sushi 1 and Sushi 3) as well as their corresponding mutants exhibited activities against 30 clinical isolates of Pseudomonas aeruginosa. Collectively, all four peptides demonstrated exceptionally effective bactericidal activity against P. aeruginosa with 90% minimal bactericidal concentrations (MBC₉₀s) in the range of 0.06 to 0.25 µg/ml (16 to 63 nM). Viable bacteria were reduced by 90% after 7 min and were totally eradicated within 40 to 50 min. These peptides are minimally hemolytic against both rabbit and human erythrocytes even at concentrations up to 1,600-fold their MBC₉₀s. Both in vitro and in vivo studies indicate that cytotoxic effects are small even at 1,000-fold their MBC₉₀s. Furthermore, the Sushi peptides are tolerant of high-salt and adverse pH conditions. These findings demonstrate the promising therapeutic potential of the Sushi peptides.

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^* Corresponding author. Mailing address: Department of Biological Sciences, National University of Singapore, Kent Ridge, Singapore 117543, Singapore. Phone: (65) 874 2776. Fax: (65) 779 2486. E-mail: dbsdjl{at}nus.edu.sg.

Present address: Institut de Biologie Animale, Université de Lausanne, CH-1015 Lausanne, Switzerland.

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Antimicrobial Agents and Chemotherapy, October 2001, p. 2820-2825, Vol. 45, No. 10
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.10.2820-2825.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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