Differential expression of the polysialyl capsule during blood-to-brain transit of neuropathogenic Escherichia coli K1.
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.
Zelmer
Andrea
A
School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
Bowen
Mark
M
Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
Jokilammi
Anne
A
Department of Medical Biochemistry and Molecular Biology, University of Turku, FI-20520 Turku, Finland.
Finne
Jukka
J
Department of Medical Biochemistry and Molecular Biology, University of Turku, FI-20520 Turku, Finland.
Luzio
J Paul
JP
Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
Taylor
Peter W
PW
School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
D000818:Animals; D016667:Bacterial Capsules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000382:microbiology*; D001921:Brain / Q000382:microbiology / Q000473:pathology; D004926:Escherichia coli / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000382:microbiology* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D051381:Rats; D017208:Rats, Wistar; D012794:Sialic Acids / Q000378:metabolism*
D012794:Sialic Acids; C021319:polysialic acid