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Logarithmic phase Escherichia coli K1 efficiently avoids serum killing by promoting C4bp-mediated C3b and C4b degradation

Wooster, DG ; Maruvada, R ; Blom, Anna LU orcid and Prasadarao, NV (2006) In Immunology 117(4). p.482-493
Abstract
Meningitis caused by Escherichia coli K1 is a serious illness in neonates with neurological sequelae in up to 50% of survivors. A high degree of bacteremia is required for E. coli K1 to cross the blood-brain barrier, which suggests that the bacterium must evade the host defence mechanisms and survive in the bloodstream. We previously showed that outer membrane protein A (OmpA) of E. coli binds C4b-binding protein (C4bp), an inhibitor of complement activation via the classical pathway. Nevertheless, the exact mechanism by which E. coli K1 survives in serum remains elusive. Here, we demonstrate that log phase (LP) OmpA(+) E. coli K1 avoids serum bactericidal activity more effectively than postexponential phase bacteria. OmpA(-)E. coli cannot... (More)
Meningitis caused by Escherichia coli K1 is a serious illness in neonates with neurological sequelae in up to 50% of survivors. A high degree of bacteremia is required for E. coli K1 to cross the blood-brain barrier, which suggests that the bacterium must evade the host defence mechanisms and survive in the bloodstream. We previously showed that outer membrane protein A (OmpA) of E. coli binds C4b-binding protein (C4bp), an inhibitor of complement activation via the classical pathway. Nevertheless, the exact mechanism by which E. coli K1 survives in serum remains elusive. Here, we demonstrate that log phase (LP) OmpA(+) E. coli K1 avoids serum bactericidal activity more effectively than postexponential phase bacteria. OmpA(-)E. coli cannot survive in serum grown to either phase. The increased serum resistance of LP OmpA(+) E. coli is the result of increased binding of C4bp, with a concomitant decrease in the deposition of C3b and the downstream complement proteins responsible for the formation of the membrane attack complex. C4bp bound to E. coli K1 acts as a cofactor to factor I in the cleavage of both C3b and C4b, which shuts down the ensuing complement cascade. Accordingly, a peptide corresponding to the complement control protein domain 3 of C4bp sequence, was able to compete with C4bp binding to OmpA and cause increased deposition of C3b. Thus, binding of C4bp appears to be responsible for survival of E. coli K1 in human serum. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
outer, meningitis, Escherichia coli K1, C4b-binding protein, complement, membrane protein A
in
Immunology
volume
117
issue
4
pages
482 - 493
publisher
Wiley-Blackwell
external identifiers
  • pmid:16556262
  • wos:000236023900007
  • scopus:33645021029
ISSN
0019-2805
DOI
10.1111/j.1365-2567.2006.02323.x
language
English
LU publication?
yes
id
9ee6c84f-36e9-4334-9af8-ecde0dbb042a (old id 415723)
date added to LUP
2016-04-01 12:21:55
date last changed
2020-10-24 02:17:58
@article{9ee6c84f-36e9-4334-9af8-ecde0dbb042a,
  abstract     = {Meningitis caused by Escherichia coli K1 is a serious illness in neonates with neurological sequelae in up to 50% of survivors. A high degree of bacteremia is required for E. coli K1 to cross the blood-brain barrier, which suggests that the bacterium must evade the host defence mechanisms and survive in the bloodstream. We previously showed that outer membrane protein A (OmpA) of E. coli binds C4b-binding protein (C4bp), an inhibitor of complement activation via the classical pathway. Nevertheless, the exact mechanism by which E. coli K1 survives in serum remains elusive. Here, we demonstrate that log phase (LP) OmpA(+) E. coli K1 avoids serum bactericidal activity more effectively than postexponential phase bacteria. OmpA(-)E. coli cannot survive in serum grown to either phase. The increased serum resistance of LP OmpA(+) E. coli is the result of increased binding of C4bp, with a concomitant decrease in the deposition of C3b and the downstream complement proteins responsible for the formation of the membrane attack complex. C4bp bound to E. coli K1 acts as a cofactor to factor I in the cleavage of both C3b and C4b, which shuts down the ensuing complement cascade. Accordingly, a peptide corresponding to the complement control protein domain 3 of C4bp sequence, was able to compete with C4bp binding to OmpA and cause increased deposition of C3b. Thus, binding of C4bp appears to be responsible for survival of E. coli K1 in human serum.},
  author       = {Wooster, DG and Maruvada, R and Blom, Anna and Prasadarao, NV},
  issn         = {0019-2805},
  language     = {eng},
  number       = {4},
  pages        = {482--493},
  publisher    = {Wiley-Blackwell},
  series       = {Immunology},
  title        = {Logarithmic phase Escherichia coli K1 efficiently avoids serum killing by promoting C4bp-mediated C3b and C4b degradation},
  url          = {http://dx.doi.org/10.1111/j.1365-2567.2006.02323.x},
  doi          = {10.1111/j.1365-2567.2006.02323.x},
  volume       = {117},
  year         = {2006},
}