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Neisseria gonorrhoeae co-opts C4b-binding protein to enhance complement-independent survival from neutrophils

Werner, Lacie M. ; Alcott, Allison ; Mohlin, Frida LU ; Ray, Jocelyn C. ; Dufrisne, Meagan Belcher ; Smirnov, Asya ; Columbus, Linda ; Blom, Anna M. LU orcid and Criss, Alison K. (2023) In PLoS Pathogens 19(3).
Abstract

Neisseria gonorrhoeae (Gc) is a human-specific pathogen that causes the sexually transmitted infection gonorrhea. Gc survives in neutrophil-rich gonorrheal secretions, and recovered bacteria predominantly express phase-variable, surface-expressed opacity-associated (Opa) proteins (Opa+). However, expression of Opa proteins like OpaD decreases Gc survival when exposed to human neutrophils ex vivo. Here, we made the unexpected observation that incubation with normal human serum, which is found in inflamed mucosal secretions, enhances survival of Opa+ Gc from primary human neutrophils. We directly linked this phenomenon to a novel complement-independent function for C4b-binding protein (C4BP). When bound to the bacteria, C4BP was necessary... (More)

Neisseria gonorrhoeae (Gc) is a human-specific pathogen that causes the sexually transmitted infection gonorrhea. Gc survives in neutrophil-rich gonorrheal secretions, and recovered bacteria predominantly express phase-variable, surface-expressed opacity-associated (Opa) proteins (Opa+). However, expression of Opa proteins like OpaD decreases Gc survival when exposed to human neutrophils ex vivo. Here, we made the unexpected observation that incubation with normal human serum, which is found in inflamed mucosal secretions, enhances survival of Opa+ Gc from primary human neutrophils. We directly linked this phenomenon to a novel complement-independent function for C4b-binding protein (C4BP). When bound to the bacteria, C4BP was necessary and sufficient to suppress Gc-induced neutrophil reactive oxygen species production and prevent neutrophil phagocytosis of Opa+ Gc. This research identifies for the first time a complement-independent role for C4BP in enhancing the survival of a pathogenic bacterium from phagocytes, thereby revealing how Gc exploits inflammatory conditions to persist at human mucosal surfaces.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Pathogens
volume
19
issue
3
article number
e1011055
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:36862761
  • scopus:85149395141
ISSN
1553-7366
DOI
10.1371/journal.ppat.1011055
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 Werner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
id
129a3e56-73ec-4e4b-8c9a-c3de8c6df0a5
date added to LUP
2024-01-12 14:19:16
date last changed
2025-05-11 20:35:55
@article{129a3e56-73ec-4e4b-8c9a-c3de8c6df0a5,
  abstract     = {{<p>Neisseria gonorrhoeae (Gc) is a human-specific pathogen that causes the sexually transmitted infection gonorrhea. Gc survives in neutrophil-rich gonorrheal secretions, and recovered bacteria predominantly express phase-variable, surface-expressed opacity-associated (Opa) proteins (Opa+). However, expression of Opa proteins like OpaD decreases Gc survival when exposed to human neutrophils ex vivo. Here, we made the unexpected observation that incubation with normal human serum, which is found in inflamed mucosal secretions, enhances survival of Opa+ Gc from primary human neutrophils. We directly linked this phenomenon to a novel complement-independent function for C4b-binding protein (C4BP). When bound to the bacteria, C4BP was necessary and sufficient to suppress Gc-induced neutrophil reactive oxygen species production and prevent neutrophil phagocytosis of Opa+ Gc. This research identifies for the first time a complement-independent role for C4BP in enhancing the survival of a pathogenic bacterium from phagocytes, thereby revealing how Gc exploits inflammatory conditions to persist at human mucosal surfaces.</p>}},
  author       = {{Werner, Lacie M. and Alcott, Allison and Mohlin, Frida and Ray, Jocelyn C. and Dufrisne, Meagan Belcher and Smirnov, Asya and Columbus, Linda and Blom, Anna M. and Criss, Alison K.}},
  issn         = {{1553-7366}},
  language     = {{eng}},
  number       = {{3}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS Pathogens}},
  title        = {{Neisseria gonorrhoeae co-opts C4b-binding protein to enhance complement-independent survival from neutrophils}},
  url          = {{http://dx.doi.org/10.1371/journal.ppat.1011055}},
  doi          = {{10.1371/journal.ppat.1011055}},
  volume       = {{19}},
  year         = {{2023}},
}