1887

Abstract

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--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.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.2008/017988-0
2008-08-01
2020-09-20
Loading full text...

Full text loading...

/deliver/fulltext/micro/154/8/2522.html?itemId=/content/journal/micro/10.1099/mic.0.2008/017988-0&mimeType=html&fmt=ahah

References

  1. Achtman M., Mercer A., Kusećek B., Pohl A., Heuzenroeder M., Aaronson W., Sutton A., Silver R. P.. 1983; Six widespread bacterial clones among Escherichia coli K1 isolates. Infect Immun39:315–335
    [Google Scholar]
  2. Bortolussi R., Ferrieri P., BjÖrkstén B., Quie P. G.. 1979; Capsular K1 polysaccharide of Escherichia coli: relationship to virulence in newborn rats and resistance to phagocytosis. Infect Immun25:293–298
    [Google Scholar]
  3. Cieslewicz M., Vimr E.. 1997; Reduced polysialic acid capsule expression in Escherichia coli K1 mutants with chromosomal defects in kpsF. Mol Microbiol26:237–249
    [Google Scholar]
  4. Colino J., Outschoorn I.. 1999; The form variation of the capsular polysaccharide K1 is not a critical virulence factor of Escherichia coli in a neonatal mouse model of infection. Microb Pathog27:187–196
    [Google Scholar]
  5. Cross A. S., Kim K. S., Wright D. C., Sadoff J. C., Gemski P.. 1986; Role of lipopolysaccharide and capsule in the serum resistance of bacteremic Escherichia coli. J Infect Dis154:497–503
    [Google Scholar]
  6. Deszo E. L., Steenbergen S. M., Freedberg D. I., Vimr E. R.. 2005; Escherichia coli K1 polysialic acid O-acetyltranferase gene, neuO, and the mechanism of capsule form variation involving a mobile contingency locus. Proc Natl Acad Sci U S A102:5564–5569
    [Google Scholar]
  7. Drury R. A. B., Wallington E. A.. 1980; Carleton's Histological Technique , 5th edn. New York: Oxford University Press;
    [Google Scholar]
  8. Fowler M. I., Weller R. O., Heckels J. E., Christodoulides M.. 2004; Different meningitis-causing bacteria induce distinct inflammatory responses on interaction with cells of the human meninges. Cell Microbiol6:555–567
    [Google Scholar]
  9. Gaudreau C., Delage G., Rousseau D., Cantor E. D.. 1981; Bacteremia caused by viridans streptococci in 71 children. Can Med Assoc J125:1246–1249
    [Google Scholar]
  10. Glode M. P., Sutton A., Moxon E. R., Robbins J. B.. 1977; Pathogenesis of neonatal Escherichia coli meningitis: induction of bacteremia and meningitis in infant rats fed E. coli K1. Infect Immun16:75–80
    [Google Scholar]
  11. Harvey D., Holt D. E., Bedford H.. 1999; Bacterial meningitis in the newborn: a prospective study of mortality and morbidity. Semin Perinatol23:218–225
    [Google Scholar]
  12. Jokilammi A., Ollikka P., Korja M., Jakobsson E., Loimaranta V., Haataja H., Finne J.. 2004; Construction of antibody mimics from a noncatalytic enzyme – detection of polysialic acid. J Immunol Methods295:149–160
    [Google Scholar]
  13. Kim K. S.. 2003; Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury. Nat Rev Neurosci4:376–385
    [Google Scholar]
  14. Kim K. S., Itabashi H., Gemski P., Sadoff J., Warren R. L., Cross A. S.. 1992; The K1 capsule is the critical determinant in the development of Escherichia coli meningitis in the rat. J Clin Invest90:897–905
    [Google Scholar]
  15. Kim B. Y., Kang J., Kim K. S.. 2005; Invasion processes of pathogenic Escherichia coli. Int J Med Microbiol295:463–470
    [Google Scholar]
  16. King M. R., Steenbergen S. M., Vimr E. R.. 2007; Going for baroque at the Escherichia coli K1 cell surface. Trends Microbiol15:196–202
    [Google Scholar]
  17. Korhonen T. K., Valtonen M. V., Parkkinen J., Väisänen-Rhen V., Finne J., Ørskov F., Ørskov I., Svenson S. B., Mäkelä P. H.. 1985; Serotypes, hemolysin production, and receptor recognition of Escherichia coli strains associated with neonatal sepsis and meningitis. Infect Immun48:486–491
    [Google Scholar]
  18. Leggate D. R., Bryant J. M., Redpath M. B., Head D., Taylor P. W., Luzio J. P.. 2002; Expression, mutagenesis and kinetic analysis of recombinant K1E endosialidase to define the site of proteolytic processing and requirements for catalysis. Mol Microbiol44:749–760
    [Google Scholar]
  19. Moody D. M.. 2006; The blood-brain barrier and blood-cerebral spinal fluid barrier. Semin Cardiothorac Vasc Anesth10:128–131
    [Google Scholar]
  20. Mühlenhoff M., Eckhardt M., Gerardy-Schahn R.. 1998; Polysialic acid: three-dimensional structure, biosynthesis and function. Curr Opin Struct Biol8:558–564
    [Google Scholar]
  21. Mushtaq N., Redpath M. B., Luzio J. P., Taylor P. W.. 2004; Prevention and cure of systemic Escherichia coli K1 infection by modification of the bacterial phenotype. Antimicrob Agents Chemother48:1503–1508
    [Google Scholar]
  22. Mushtaq N., Redpath M. B., Luzio J. P., Taylor P. W.. 2005; Treatment of experimental Escherichia coli infection with recombinant bacteriophage-derived capsule depolymerase. J Antimicrob Chemother56:160–165
    [Google Scholar]
  23. Nassif X., Bourdoulous S., Eugène E., Couraud P.-O.. 2002; How do extracellular pathogens cross the blood-brain barrier?. Trends Microbiol10:227–232
    [Google Scholar]
  24. Ørskov F., Ørskov I., Sutton A., Schneerson R., Lin W., Egan W., Hoff G. E., Robbins J. B.. 1979; Form variation in Escherichia coli K1: determined by O-acetylation of the capsular polysaccharide. J Exp Med149:669–685
    [Google Scholar]
  25. Palmer C., Bik E. M., DiGiulio D. B., Relman D. A., Brown P. O.. 2007; Development of the human infant intestinal microbiota. PLoS Biol5:e177
    [Google Scholar]
  26. Parkkinen J., Korhonen T. K., Pere A., Hacker J., Soinila S.. 1988; Binding sites in the rat brain for Escherichia coli S fimbriae associated with neonatal meningitis. J Clin Invest81:860–865
    [Google Scholar]
  27. Paxinos G., Wilson C.. 2007; The Rat Brain in Stereotaxic Coordinates , 6th edn. London: Academic Press;
    [Google Scholar]
  28. Pluschke G., Mercer A., Kusećek B., Pohl A., Achtman M.. 1983; Induction of bacteremia in newborn rats by Escherichia coli K1 is correlated with only certain O (lipopolysaccharide) antigen types. Infect Immun39:599–608
    [Google Scholar]
  29. Polin R. A., Harris M. C.. 2001; Neonatal bacterial meningitis. Semin Neonatol6:157–172
    [Google Scholar]
  30. Robbins J. B., McCracken G. H., Gotschlich E. C., Ørskov F., Ørskov I., Hanson L. A.. 1974; Escherichia coli K1 capsular polysaccharide associated with neonatal meningitis. N Engl J Med290:1216–1220
    [Google Scholar]
  31. Saunders N. R., Knott G. W., Dziegelewska K. M.. 2000; Barriers in the immature brain. Cell Mol Neurobiol20:29–40
    [Google Scholar]
  32. Siegel J. D., McCracken G. H.. 1981; Sepsis neonatorum. N Engl J Med304:642–647
    [Google Scholar]
  33. Steenbergen S. M., Lee Y.-C., Vann W. F., Vionnet J., Wright L. F., Vimr E. R.. 2006; Separate pathways for O-acetylation of polymeric and monomeric sialic acids and identification of sialyl O-acetyl esterase in Escherichia coli K1. J Bacteriol188:6195–6206
    [Google Scholar]
  34. Stein D. M., Robbins J., Miller M. A., Lin F.-Y. C., Schneerson R.. 2006; Are antibodies to the capsular polysaccharide of Neisseria meningitidis group B and Escherichia coli K1 associated with immunopathology?. Vaccine24:221–228
    [Google Scholar]
  35. Taylor P. W.. 1993; Non-immunoglobulin activators of the complement system. In Activators and Inhibitors of Complement. pp37–68 Edited by Sim R. B. Dordrecht, The Netherlands: Kluwer Academic Publishers;
  36. Taylor P. W., Stapleton P. D., Luzio J. P.. 2002; New ways to treat bacterial infections. Drug Discov Today7:1086–1091
    [Google Scholar]
  37. Tomlinson S., Taylor P. W.. 1985; Neuraminidase associated with coliphage E that specifically depolymerizes the Escherichia coli K1 capsular polysaccharide. J Virol55:374–378
    [Google Scholar]
  38. Tunkel A. R., Scheld W. M.. 1993; Pathogenesis and pathophysiology of bacterial meningitis. Clin Microbiol Rev6:118–136
    [Google Scholar]
  39. Vimr E. R., Steenbergen S. M.. 2006; Mobile contingency locus controlling Escherichia coli polysialic acid capsule acetylation. Mol Microbiol60:828–837
    [Google Scholar]
  40. Vimr E. R., Troy F. A.. 1985; Identification of an inducible catabolic system for sialic acids (nan) in Escherichia coli. J Bacteriol164:845–853
    [Google Scholar]
  41. Weinhold B., Seidenfaden R., RÖckle I., Mühlenhoff M., Schertzinger F., Conzelmann S., Marth J. D., Gerardy-Schahn R., Hildebrandt H.. 2005; Genetic ablation of polysialic acid causes severe neurodevelopmental defects rescued by deletion of the neural cell adhesion molecule. J Biol Chem280:42971–42977
    [Google Scholar]
  42. Xie Y., Kim K. J., Kim K. S.. 2004; Current concepts on Escherichia coli K1 translocation of the blood-brain barrier. FEMS Immunol Med Microbiol42:271–279
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.2008/017988-0
Loading
/content/journal/micro/10.1099/mic.0.2008/017988-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error