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Citations to this article

C4BP-IgM protein as a therapeutic approach to treat Neisseria gonorrhoeae infections
Serena Bettoni, … , Sanjay Ram, Anna M. Blom
Serena Bettoni, … , Sanjay Ram, Anna M. Blom
Published October 29, 2019
Citation Information: JCI Insight. 2019;4(23):e131886. https://doi.org/10.1172/jci.insight.131886.
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Research Article Infectious disease Therapeutics Article has an altmetric score of 7

C4BP-IgM protein as a therapeutic approach to treat Neisseria gonorrhoeae infections

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Abstract

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.

Authors

Serena Bettoni, Jutamas Shaughnessy, Karolina Maziarz, David Ermert, Sunita Gulati, Bo Zheng, Matthias Mörgelin, Susanne Jacobsson, Kristian Riesbeck, Magnus Unemo, Sanjay Ram, Anna M. Blom

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 Total
Citations: 3 3 7 3 6 1 23
Citation information
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Citations to this article in year 2025 (3)

Title and authors Publication Year
Terminal complement complexes with or without C9 potentiate antimicrobial activity against Neisseria gonorrhoeae
Lamb ER, Criss AK
bioRxiv 2025
Acinetobacter baumannii Clinical Isolates Resist Complement-Mediated Lysis by Inhibiting the Complement Cascade and Improperly Depositing MAC
Magda M, Boschloo W, Bettoni S, Fairley D, Russo TA, Giske CG, Tellapragada C, Rooijakkers SH, Riesbeck K, Blom AM
Journal of Innate Immunity 2025
Terminal complement complexes with or without C9 potentiate antimicrobial activity against Neisseria gonorrhoeae.
Lamb ER, Criss AK
mBio 2025

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