J. Colino et I. Outschoorn, The form variation of the capsular polysaccharide K1 is not a critical virulence factor of Escherichia coli in a neonatal mouse model of infection, MICROB PATH, 27(4), 1999, pp. 187-196
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.