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Antimicrobial Agents and Chemotherapy, May 2004, p. 1503-1508, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1503-1508.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Prevention and Cure of Systemic Escherichia coli K1 Infection by Modification of the Bacterial Phenotype

Naseem Mushtaq,1 Maria B. Redpath,1 J. Paul Luzio,2 and Peter W. Taylor1*

Microbiology Group, School of Pharmacy, London WC1N 1AX,1 Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge CB2 2XY, United Kingdom2

Received 6 October 2003/ Returned for modification 3 December 2003/ Accepted 20 January 2004

Escherichia coli is a common cause of meningitis and sepsis in the newborn infant, and the large majority of isolates from these infections produce a polysialic acid (PSA) capsular polysaccharide, the K1 antigen, that protects the bacterial cell from immune attack. We determined whether a capsule-depolymerizing enzyme, by removing this protective barrier, could alter the outcome of systemic infection in an animal model. Bacteriophage-derived endosialidase E (endoE) selectively degrades the PSA capsule on the surface of E. coli K1 strains. Intraperitoneal administration of small quantities of recombinant endoE (20 µg) to 3-day-old rats, colonized with a virulent strain of K1, prevented bacteremia and death from systemic infection. The enzyme had no effect on the viability of E. coli strains but sensitized strains expressing PSA to killing by the complement system. This study demonstrates the potential therapeutic efficacy of agents that cure infections by modification of the bacterial phenotype rather than by killing or inhibition of growth of the pathogen.

* Corresponding author. Mailing address: Department of Pharmaceutics, School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom. Phone: 44-20-7753-5867. Fax: 44-20-7753-5867. E-mail: peter.taylor{at}ulsop.ac.uk.

Antimicrobial Agents and Chemotherapy, May 2004, p. 1503-1508, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1503-1508.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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