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Serum Complement Ac...
Serum Complement Activation by C4BP-IgM Fusion Protein Can Restore Susceptibility to Antibiotics in Neisseria gonorrhoeae
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- Bettoni, Serena (author)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Maziarz, Karolina (author)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Stone, M. Rhia L. (author)
- Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
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- Blaskovich, Mark A. T. (author)
- Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
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- Potempa, Jan (author)
- Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; Department of Oral Immunity and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United States,University of Louisville Health Sciences Center
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- Bazzo, Maria Luiza (author)
- Molecular Biology, Microbiology and Serology Laboratory, Federal University of Santa Catarina, Florianópolis, Brazil
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- Unemo, Magnus, 1970- (author)
- Örebro University,Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,World Health Organization (WHO) Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine
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- Ram, Sanjay (author)
- Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, MA, United States
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- Blom, Anna M. (author)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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(creator_code:org_t)
- 2021-09-01
- 2021
- English.
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
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Abstract
Subject headings
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- Neisseria gonorrhoeae is the etiological agent of gonorrhea, the second most common bacterial sexually transmitted infection worldwide. Reproductive sequelae of gonorrhea include infertility, ectopic pregnancy and chronic pelvic pain. Most antibiotics currently in clinical use have been rendered ineffective due to the rapid spread of antimicrobial resistance among gonococci. The developmental pipeline of new antibiotics is sparse and novel therapeutic approaches are urgently needed. Previously, we utilized the ability of N. gonorrhoeae to bind the complement inhibitor C4b-binding protein (C4BP) to evade killing by human complement to design a chimeric protein that linked the two N-terminal gonococcal binding domains of C4BP with the Fc domain of IgM. The resulting molecule, C4BP-IgM, enhanced complement-mediated killing of gonococci. Here we show that C4BP-IgM induced membrane perturbation through complement deposition and membrane attack complex pore insertion facilitates the access of antibiotics to their intracellular targets. Consequently, bacteria become more susceptible to killing by antibiotics. Remarkably, C4BP-IgM restored susceptibility to azithromycin of two azithromycin-resistant clinical gonococcal strains because of overexpression of the MtrC-MtrD-MtrE efflux pump. Our data show that complement activation can potentiate activity of antibiotics and suggest a role for C4BP-IgM as an adjuvant for antibiotic treatment of drug-resistant gonorrhea.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Keyword
- C4b binding protein
- Neisseria gonorrhoeae
- antibiotic resisitance
- complement
- membrane attack complex (MAC)
- antibiotic resisitance
- C4b binding protein
- complement
- membrane attack complex (MAC)
- Neisseria gonorrhoeae
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Bettoni, Serena
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Maziarz, Karolin ...
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Stone, M. Rhia L ...
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Blaskovich, Mark ...
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Potempa, Jan
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Bazzo, Maria Lui ...
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Unemo, Magnus, 1 ...
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Ram, Sanjay
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Blom, Anna M.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
- Articles in the publication
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Frontiers in Imm ...
- By the university
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Örebro University
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Lund University