To Örebro University

oru.seÖrebro University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
C4BP-IgM protein as a therapeutic approach to treat Neisseria gonorrhoeae infections
Department of Translational Medicine, Lund University, Malmö, Sweden.
Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Department of Translational Medicine, Lund University, Malmö, Sweden.
Department of Translational Medicine, Lund University, Malmö, Sweden.
Show others and affiliations
2019 (English)In: JCI Insight, ISSN 2379-3708, Vol. 4, no 23, article id 131886Article in journal (Refereed) Published
Abstract [en]

Gonorrhea is a sexually transmitted infection with 87 million new cases per year globally. Increasing antibiotic resistance has severely limited treatment options. A mechanism that Neisseria gonorrhoeae uses to evade complement attack is binding of the complement inhibitor C4b-binding protein (C4BP). We screened 107 porin B1a (PorB1a) and 83 PorB1b clinical isolates randomly selected from a Swedish strain collection over the last 10 years and noted that 96/107 (89.7%) PorB1a and 16/83 (19.3%) PorB1b bound C4BP; C4BP binding substantially correlated with the ability to evade complement-dependent killing (r = 0.78). We designed 2 chimeric proteins that fused C4BP domains to the backbone of IgG or IgM (C4BP-IgG; C4BP-IgM) with the aim of enhancing complement activation and killing of gonococci. Both proteins bound gonococci (KD C4BP-IgM = 2.4 nM; KD C4BP-IgG 980.7 nM), but only hexameric C4BP-IgM efficiently outcompeted heptameric C4BP from the bacterial surface, resulting in enhanced complement deposition and bacterial killing. Furthermore, C4BP-IgM substantially attenuated the duration and burden of colonization of 2 C4BP-binding gonococcal isolates but not a non-C4BP-binding strain in a mouse vaginal colonization model using human factor H/C4BP-transgenic mice. Our preclinical data present C4BP-IgM as an adjunct to conventional antimicrobials for the treatment of gonorrhea.

Place, publisher, year, edition, pages
American Society for Clinical Investigation (ASCI) , 2019. Vol. 4, no 23, article id 131886
Keywords [en]
Bacterial infections, Complement, Immunotherapy, Infectious disease, Therapeutics
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:oru:diva-78562DOI: 10.1172/jci.insight.131886ISI: 000500946900014PubMedID: 31661468Scopus ID: 2-s2.0-85077586369OAI: oai:DiVA.org:oru-78562DiVA, id: diva2:1378550
Funder
Swedish Research Council Formas, 2018-02392
Note

Funding Agencies:

United States Department of Health & Human Services

National Institutes of Health (NIH) - USA AI119327 AI114790 AI132296 AI147930 AI136007

Söderberg Foundation  

Österlund Foundation  

Royal Physiographic Society of Lund  

Sten K. Johnsons Foundation 

Available from: 2019-12-13 Created: 2019-12-13 Last updated: 2023-12-08Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records

Unemo, Magnus

Search in DiVA

By author/editor
Unemo, Magnus
By organisation
School of Medical SciencesÖrebro University Hospital
In the same journal
JCI Insight
Infectious Medicine

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 70 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf