1887

Abstract

Many neurotropic strains of cause potentially lethal bacteraemia and meningitis in newborn infants by virtue of their capacity to elaborate the protective polysialic acid (polySia) K1 capsule. Recombinant capsule depolymerase, endosialidase E (endoE), selectively removes polySia from the bacterial surface; when administered intraperitoneally to infected neonatal rats, the enzyme interrupts the transit of K1 from gut to brain via the blood circulation and prevents death from systemic infection. We now show that experimental K1 infection is accompanied by extensive modulation of host gene expression in the liver, spleen and brain tissues of neonatal rats. Bacterial invasion of the brain resulted in a threefold or greater upregulation of approximately 400 genes, a large number of which were associated with the induction of inflammation and the immune and stress responses: these included genes encoding C–X–C and C–C chemokines, lipocalins, cytokines, apolipoproteins and enzymes involved in the synthesis of low-molecular-mass inflammatory mediators. Administration of a single dose of endoE, 24 h after initiation of systemic infection, markedly reduced, but did not completely abrogate, these changes in gene expression, suggesting that attenuation of K1 virulence by removal of the polySia capsule may minimize the attendant inflammatory processes that contribute to poor outcome in these severe systemic infections.

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2010-07-01
2019-10-14
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vol. , part 7, pp. 2205 - 2215

( PDF, 61 kb): Forward and reverse primer pairs for amplification of genes examined using qRT-PCR for validation of microarray results Genes in neonatal rat liver altered in response to infection with K1 Genes in neonatal rat spleen altered in response to infection with K1 Genes upregulated more than threefold in neonatal rat liver following administration of 20 μg endoE to uninfected pups at P3 Genes upregulated more than threefold in neonatal rat spleen following administration of 20 μg endoE to uninfected pups at P3



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