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Antimicrobial Agents and Chemotherapy, November 2005, p. 4561-4566, Vol. 49, No. 11
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.11.4561-4566.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Antibacterial Activity of Human Neutrophil Defensin HNP-1 Analogs without Cysteines

Jobin Varkey and Ramakrishnan Nagaraj*

Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India

Received 7 February 2005/ Returned for modification 9 April 2005/ Accepted 15 August 2005

The antibacterial activity of human neutrophil defensin HNP-1 analogs without cysteines has been investigated. A peptide corresponding to the HNP-1 sequence without the six cysteines (HNP-1{Delta}C) exhibited antibacterial activity toward gram-negative and gram-positive bacteria. Truncated analogs wherein the nine N-terminal residues of HNP-1 and the remaining three cysteines were deleted (HNP-1{Delta}C18) or the G was replaced with A (HNP-1{Delta}C18A) also exhibited antibacterial activity. Substantial activity was observed for HNP-1{Delta}C and HNP-1{Delta}C18 in the presence of 100 mM NaCl, except in the case of Pseudomonas aeruginosa. The linear peptides were active in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), indicating that proton motive force was not essential for killing of bacteria by the peptides. In fact, in the presence of CCCP, the peptides were active against P. aeruginosa even in the presence of 100 mM NaCl. The antibacterial activity of HNP-1{Delta}C, but not that of the shorter, 18-residue peptides, was attenuated in the presence of serum. The generation of defensins without cysteines would be easier than that of disulfide-linked defensins. Hence, linear defensins could have potential as therapeutic agents.


* Corresponding author. Mailing address: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India. Phone: 91-40-27192589. Fax: 91-40-27160591/27160311. E-mail: nraj{at}ccmb.res.in.


Antimicrobial Agents and Chemotherapy, November 2005, p. 4561-4566, Vol. 49, No. 11
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.11.4561-4566.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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