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  • Bettoni, SerenaLund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups (författare)

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

  • Artikel/kapitelEngelska2019

Förlag, utgivningsår, omfång ...

  • 2019-12-05
  • American Society for Clinical Investigation (ASCI),2019
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:oru-78562
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-78562URI
  • https://doi.org/10.1172/jci.insight.131886DOI
  • https://lup.lub.lu.se/record/61674b80-3f64-4f3c-bd63-3d195c96752dURI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies:United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA AI119327 AI114790 AI132296 AI147930 AI136007Söderberg Foundation  Österlund Foundation  Royal Physiographic Society of Lund  Sten K. Johnsons Foundation 
  • 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 och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Shaughnessy, JutamasDepartment of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA (författare)
  • Maziarz, KarolinaLund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups(Swepub:lu)ka2310ma (författare)
  • Ermert, DavidLund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups(Swepub:lu)med-dve (författare)
  • Gulati, SunitaDepartment of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA (författare)
  • Zheng, BoDepartment of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA (författare)
  • Mörgelin, MatthiasLund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups(Swepub:lu)klke-abl (författare)
  • Jacobsson, SusanneÖrebro University,Örebro University Hospital (författare)
  • Riesbeck, KristianLund University,Lunds universitet,Klinisk mikrobiologi, Malmö,Forskargrupper vid Lunds universitet,Clinical Microbiology, Malmö,Lund University Research Groups(Swepub:lu)mikr-kri (författare)
  • Unemo, Magnus,1970-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(Swepub:oru)muo (författare)
  • Ram, SanjayDepartment of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, Massachusetts, USA (författare)
  • Blom, Anna M.Department of Translational Medicine, Lund University, Malmö, Sweden (författare)
  • Proteinkemi, MalmöForskargrupper vid Lunds universitet (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:JCI Insight: American Society for Clinical Investigation (ASCI)4:232379-3708

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