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.