The capsule supports survival but not traversal of Escherichia coli K1 across the blood-brain barrier

The vast majority of cases of gram-negative meningitis in neonates are caus ed by K1-encapsulated Escherichia coli. The role of the K1 capsule in the p athogenesis of E. coli meningitis was examined with an in vivo model of exp erimental hematogenous E. coil K1 meningitis and an in vitro model of the b lood-brain barrier. Bacteremia was induced in neonatal rats with the E. col i EU strain C5 (O18:K1) or its K1(-) derivative, C5ME, Subsequently, blood and cerebrospinal fluid (CSF) were obtained for culture. Viable bacteria we re recovered from the CSF of animals infected with E. coli K1 strains only; none of the animals infected with K1(-) strains had positive CSF cultures. However, despite the fact that their cultures were sterile, the presence o f O18 E. coil was demonstrated immunocytochemically in the brains of animal s infected with K1(-) strains and was seen by staining of CSF samples. Zn v itro, brain microvascular endothelial cells (BMEC) were incubated with K1() and K1(-) E. coli strains. The recovery of viable intracellular organisms of the K1(+) strain was significantly higher than that for the K1(-) strai n (P = 0.0005). The recovery of viable intracellular K1(-) E. coli bacteria was increased by cycloheximide treatment of BMEC (P = 0.0059) but was not affected by nitric oxide synthase inhibitors or oxygen radical scavengers. We conclude that the K1 capsule is not necessary for the invasion of bacter ia into brain endothelial cells but is responsible for helping to maintain bacterial viability during invasion of the blood-brain barrier.