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Antimicrobial Agents and Chemotherapy, May 2008, p. 1812-1819, Vol. 52, No. 5
0066-4804/08/$08.00+0     doi:10.1128/AAC.01530-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Enhanced Resistance to Bacterial Infection in Protegrin-1 Transgenic Mice

Department of Animal and Poultry Science, Ontario Agriculture College,¹ Department of Pathobiology, Ontario Veterinary College,² Animal Health Laboratory, University of Guelph, Guelph, Ontario, Canada³

Received 27 November 2007/ Returned for modification 17 February 2008/ Accepted 24 February 2008

Antibiotic-resistant bacteria have become a public health concern. It was suggested that one source of resistant pathogens may be food-producing animals. Alternative approaches are therefore needed to enhance the resistance of farm animals to bacterial infection. Protegrin-1 (PG-1) is a neutrophil-derived antimicrobial peptide that possesses activity against a wide range of bacteria and enveloped viruses. Here we report on the production of transgenic mice that ectopically expressed PG-1 and compare their susceptibilities to Actinobacillus suis infection with those of their wild-type (WT) littermates. Of the 126 mice that were challenged with A. suis, 87% of the transgenic mice survived, whereas 31% of their WT littermates survived. The PG-1 transgenic mice had significantly lower bacterial loads in their lungs and reduced numbers of pulmonary pathological lesions. The antimicrobial function of PG-1 was confirmed in vitro by using fibroblast cells isolated from the transgenic mice but not the WT mice. Moreover, differential blood cell counts in bronchoalveolar lavage fluid indicated greater number of neutrophils in PG-1 transgenic mice than in their WT littermates after bacterial challenge. Our data suggest that the ectopic expression of PG-1 in mice confers enhanced resistance to bacterial infection, laying the foundation for the development of livestock with improved resistance to infection.

Published ahead of print on 3 March 2008.