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Volume 156, Issue 7

Administration of capsule-selective endosialidase E minimizes upregulation of organ gene expression induced by experimental systemic infection with K1 Free

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.

  • Received:
  • Accepted:
  • Revised:
  • Published Online:
Keyword(s): CNS, central nervous system , CSF, cerebrospinal fluid , endoE, endosialidase E , GC-RMA, GeneChip robust multiarray averaging , GI, gastrointestinal , i.p., intraperitoneal , NBM, neonatal bacterial meningitis , polySia, polysialic acid and qRT-PCR, quantitative RT-PCR
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2010-07-01
2024-04-18
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Administration of capsule-selective endosialidase E minimizes upregulation of organ gene expression induced by experimental systemic infection with Escherichia coli K1
Microbiology 156, 2205 (2010); https://doi.org/10.1099/mic.0.036145-0
/content/journal/micro/10.1099/mic.0.036145-0
/content/journal/micro/10.1099/mic.0.036145-0
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