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Antimicrobial Agents and Chemotherapy, July 2005, p. 2972-2978, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2972-2978.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Peptides Selected for Binding to a Virulent Strain of Haemophilus influenzae by Phage Display Are Bactericidal

Sharon L. Bishop-Hurley,1 Francis J. Schmidt,2 Alice L. Erwin,3 and Arnold L. Smith3*

CSIRO Livestock Industries, P.O. Box 5545, Rockhampton, Queensland 4702, Australia,1 Department of Biochemistry, University of Missouri, Columbia, Missouri 65212,2 Seattle Biomedical Research Institute, 307 Westlake Ave. North, Ste. 500, Seattle, Washington 981093

Received 15 December 2004/ Returned for modification 15 February 2005/ Accepted 23 March 2005

Nontypeable Haemophilus influenzae (NTHi) is an obligate parasite of the oropharynx of humans, in whom it commonly causes mucosal infections such as otitis media, sinusitis, and bronchitis. We used a subtractive phage display approach to affinity select for peptides binding to the cell surface of a novel invasive NTHi strain R2866 (also called Int1). Over half of the selected phage peptides tested were bactericidal toward R2866 in a dose-dependent manner. Five of the clones encoded the same peptide sequence (KQRTSIRATEGCLPS; clone hi3/17), while the remaining four clones encoded unique peptides. All of the bactericidal phage peptides but one were cationic and had similar physical-chemical properties. Clone hi3/17 possessed a similar level of activity toward a panel of clinical NTHi isolates and H. influenzae type b strains but lacked bactericidal activity toward gram-positive (Enterococcus faecalis, Staphylococcus aureus) and gram-negative (Proteus mirabilis, Pseudomonas aeruginosa, and Salmonella enterica) bacteria. These data indicate that peptides binding to bacterial surface structures isolated by phage display may prove of value in developing new antibiotics.


* Corresponding author. Mailing address: Seattle Biomedical Research Institute, 307 Westlake Ave. North, Ste. 500, Seattle, WA 98109-5219. Phone: (206) 256-7313. Fax: (206) 256-7229. E-mail: arnold.smith{at}sbri.org.


Antimicrobial Agents and Chemotherapy, July 2005, p. 2972-2978, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2972-2978.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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