Prevention and cure of systemic Escherichia coli K1 infection by modification of the bacterial phenotype.
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 micro g) 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.
Mushtaq
Naseem
N
Microbiology Group, School of Pharmacy, London WC1N 1AX, United Kingdom.
Redpath
Maria B
MB
Luzio
J Paul
JP
Taylor
Peter W
PW
D000818:Animals; D000831:Animals, Newborn; D000942:Antigens, Bacterial / Q000378:metabolism*; D016667:Bacterial Capsules; D001435:Bacteriophages / Q000235:genetics; D003165:Complement System Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000628:therapy*; D020814:Meningitis, Escherichia coli / Q000628:therapy*; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D010957:Plasmids / Q000235:genetics; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
D000942:Antigens, Bacterial; D011135:Polysaccharides, Bacterial; D011994:Recombinant Proteins; C036962:capsular polysaccharide K1; D003165:Complement System Proteins; C035355:endo-N-acetylneuraminidase; D009439:Neuraminidase