title: The form variation of the capsular polysaccharide K1 is not a critical virulence factor of Escherichia coli in a neonatal mouse model of infection.
abstract: Escherichia coli K1 is a prevalent cause of Gram-negative neonatal bacteraemia and meningitis in humans. Its capsular polysaccharide K1 (CpsK1) has been identified as an important virulence factor. Nevertheless, the biological and pathogenic implications of its O-acetylated and non-O-acetylated forms are poorly understood. In an attempt to address this, we monitored the expression of both CpsK1 form variants in a neonatal mouse infection model. In the absence of anti-CpsK1 antibodies, no CpsK1 form variant selection was observed during the course of infection. The administration of monoclonal antibodies specific for CpsK1 provided a high level of protection. The monoclonal antibodies that recognized both CpsK1 forms (MGB12) provided protection from up to 850 LD(50). By contrast, the administration of the monoclonal antibodies (MGB15) specific for non-O-acetylated CpsK1 cleared only bacteria expressing this CpsK1 form; a few mouse pups remained bacteraemic, and the bacteria in the blood had O-acetylated CpsK1. In those pups, the infection progressed in a similar fashion to that in mice not treated with monoclonal antibody. Moreover, when the number of bacteria expressing the O-acetylated CpsK1 in the inoculated dose is considered independently, the LD(50)was similar to that for the original strain in pups that had not been treated with monoclonal antibodies (35 CFU). These results suggest that whereas variation in acetylation form per se does not reinforce virulence, it could enable E. coli to avoid immune defenses. This highlights the importance of using highly specific monoclonal antibodies in immunotherapeutic approaches to E. coli K1 neonatal meningitis.
authors.affiliation: Immunology Service, Centro Nacional de Microbiología (C.N.M.), Madrid, Majadahonda, 28220, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Colino
authors.forename: I
authors.initials: I
authors.lastname: Outschoorn
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use; D000918:Antibody Specificity; D000940:Antigenic Variation; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D016470:Bacteremia / Q000382:microbiology; D016667:Bacterial Capsules; D004926:Escherichia coli / Q000378:metabolism / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000517:prevention & control; D007075:Immunoglobulin M / Q000378:metabolism; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D009345:Neisseria meningitidis / Q000737:chemistry; D011135:Polysaccharides, Bacterial / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014774:Virulence
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D007075:Immunoglobulin M; D011135:Polysaccharides, Bacterial; C036962:capsular polysaccharide K1