The form variation of the capsular polysaccharide K1 is not a critical virulence factor of Escherichia coli in a neonatal mouse model of infection

Escherichia coli K1 is a prevalent cause of Gram-negative neonatal bacterae mia and meningitis in humans. Its capsular polysaccharide K1 (CpsK1) has be en identified as an important virulence factor. Nevertheless, the biologica l and pathogenic implications of its O-acetylated and non-O-acetylated form s are poorly understood. In an attempt to address this, we monitored the ex pression of both CpsK1 form variants in a neonatal mouse infection model. I n 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 mono clonal antibodies that recognized both CpsK1 forms (MGB12) provided protect ion from up to 850 LD50. By contrast, the administration of the monoclonal antibodies (MGB15) specific for non-O-acetylated CpsK1 cleared only bacteri a expressing this CpsK1 form; a few mouse pups remained bacteraemic, and th e bacteria in the blood had O-acetylated CpsK1. In those pups, the infectio n progressed in a similar fashion to that in mice not treated with monoclon al antibody. Moreover, when the number of bacteria expressing the O-acetyla ted CpsK1 in the inoculated dose is considered independently, the LD50 was similar to that for the original strain in pups that had not been treated w ith monoclonal antibodies (35 CFU). These results suggest that whereas vari ation in acetylation form per se does not reinforce virulence, it could ena ble E. coli to avoid immune defenses. This highlights the importance of usi ng highly specific monoclonal antibodies in immunotherapeutic approaches to E. coli K1 neonatal meningitis. (C) 1999 Academic Press.