Escherichia coli K1 isolates synthesize a
polysialic acid (
polySia)
capsule, are components of the adult gastrointestinal microbiota and may cause lethal bacteraemia and
meningitis if acquired maternally by newborn infants. We used a neonatal rat pup K1
infection model to establish that prompt administration of a selective
capsule depolymerase reverses the bacteraemic state and prevents death of almost all pups. In untreated animals, bacteria colonize the gastrointestinal tract and gain entry to the blood compartment, where they express the non-O-acetylated form of
polySia. The bacteria invade the major organs of the host; histological and histochemical analysis of brain sections revealed that at least some bacteria enter the central nervous system through the blood-cerebrospinal fluid barrier at the choroid plexus prior to colonization of the meninges. Once in this location, they cease expression of
polySia. The unexpected abrogation of
polySia,
a factor associated with the pathogenesis of
meningitis and essential for transit through the blood, suggests that the neuropathogen dispenses with its protective
capsule once it has colonized protected niches. Thus, systemic
infections due to encapsulated pathogens may be resolved by
capsule depolymerization only if the
enzyme modifies the bacteria whilst they are in the blood compartment.