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C4BP-IgM protein as...
C4BP-IgM protein as a therapeutic approach to treat Neisseria gonorrhoeae infections
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- Bettoni, Serena (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Shaughnessy, Jutamas (författare)
- Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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- Maziarz, Karolina (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Ermert, David (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Gulati, Sunita (författare)
- Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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- Zheng, Bo (författare)
- Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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- Mörgelin, Matthias (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Jacobsson, Susanne (författare)
- Örebro University,Örebro University Hospital
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- Riesbeck, Kristian (författare)
- Lund University,Lunds universitet,Klinisk mikrobiologi, Malmö,Forskargrupper vid Lunds universitet,Clinical Microbiology, Malmö,Lund University Research Groups
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- Unemo, Magnus, 1970- (författare)
- 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,Örebro University Hospital
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- Ram, Sanjay (författare)
- Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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- Blom, Anna M. (författare)
- Department of Translational Medicine, Lund University, Malmö, Sweden
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(creator_code:org_t)
- 2019-12-05
- 2019
- Engelska.
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Ingår i: JCI Insight. - : American Society for Clinical Investigation (ASCI). - 2379-3708. ; 4:23
- Relaterad länk:
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https://doi.org/10.1...
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http://insight.jci.o...
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Nyckelord
- Bacterial infections
- Complement
- Immunotherapy
- Infectious disease
- Therapeutics
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Bettoni, Serena
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Shaughnessy, Jut ...
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Maziarz, Karolin ...
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Ermert, David
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Gulati, Sunita
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Zheng, Bo
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visa fler...
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Mörgelin, Matthi ...
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Jacobsson, Susan ...
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Riesbeck, Kristi ...
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Unemo, Magnus, 1 ...
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Ram, Sanjay
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Blom, Anna M.
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Infektionsmedici ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Mikrobiologi ino ...
- Artiklar i publikationen
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JCI Insight
- Av lärosätet
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Örebro universitet
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Lunds universitet