title: The capsule supports survival but not traversal of Escherichia coli K1 across the blood-brain barrier.
abstract: The vast majority of cases of gram-negative meningitis in neonates are caused by K1-encapsulated Escherichia coli. The role of the K1 capsule in the pathogenesis of E. coli meningitis was examined with an in vivo model of experimental hematogenous E. coli K1 meningitis and an in vitro model of the blood-brain barrier. Bacteremia was induced in neonatal rats with the E. coli K1 strain C5 (O18:K1) or its K1(-) derivative, C5ME. Subsequently, blood and cerebrospinal fluid (CSF) were obtained for culture. Viable bacteria were 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 of O18 E. coli was demonstrated immunocytochemically in the brains of animals infected with K1(-) strains and was seen by staining of CSF samples. In vitro, 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(-) strain (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 bacteria into brain endothelial cells but is responsible for helping to maintain bacterial viability during invasion of the blood-brain barrier.
authors.affiliation: Division of Infectious Diseases, Children's Hospital Los Angeles, Los Angeles, California 90027, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Hoffman
authors.forename: C
authors.initials: C
authors.lastname: Wass
authors.forename: M F
authors.initials: MF
authors.lastname: Stins
authors.forename: K S
authors.initials: KS
authors.lastname: Kim
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000502:physiology*; D001812:Blood-Brain Barrier; D004926:Escherichia coli / Q000472:pathogenicity / Q000502:physiology*; D004927:Escherichia coli Infections / Q000382:microbiology*; D007150:Immunohistochemistry; D016920:Meningitis, Bacterial / Q000382:microbiology*; D051381:Rats; D017207:Rats, Sprague-Dawley