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dc.contributor.authorLewis, Lisa A.
dc.contributor.authorRam, Sanjay
dc.contributor.authorPrasad, Alpana
dc.contributor.authorGulati, Sunita
dc.contributor.authorGetzlaff, Silke
dc.contributor.authorBlom, Anna M.
dc.contributor.authorVogel, Ulrich
dc.contributor.authorRice, Peter A
dc.date2022-08-11T08:09:32.000
dc.date.accessioned2022-08-23T16:34:43Z
dc.date.available2022-08-23T16:34:43Z
dc.date.issued2007-11-07
dc.date.submitted2009-03-16
dc.identifier.citationInfect Immun. 2008 Jan;76(1):339-50. Epub 2007 Nov 5. <a href="http://dx.doi.org/10.1128/IAI.00613-07">Link to article on publisher's site</a>
dc.identifier.issn1098-5522 (Electronic)
dc.identifier.doi10.1128/IAI.00613-07
dc.identifier.pmid17984207
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38397
dc.description.abstractComplement is a key arm of the innate immune defenses against the pathogenic neisseriae. We previously identified lipooligosaccharide on Neisseria meningitidis as an acceptor for complement C4b. Little is known about other neisserial targets for complement proteins C3 and C4, which covalently attach to bacterial surfaces and initiate opsonization and killing. In this study we demonstrate that Neisseria gonorrhoeae porin (Por) 1B selectively binds C4b via amide linkages and C3b via ester linkages. Using strains expressing hybrid Por1A/1B molecules, a region spanned by loops 4 and 5 of Por1B was identified as the preferred binding site for C4b. We also identified the opacity protein (Opa), a major adhesin of pathogenic neisseriae, as a target for C4b and C3b on both N. meningitidis and N. gonorrhoeae. Using N. gonorrhoeae variants that predominantly expressed individual Opa proteins, we found that all Opa proteins tested (A, B, C, D, E, F, and I) bound C4b and C3b via amide and ester linkages, respectively. Amide linkages with Por1B and Opa were confirmed using serum containing only the C4A isoform, which exclusively forms amide linkages with targets. While monomers and heterodimers of C4Ab were detected on bacterial targets, C4Bb appeared to preferentially participate in heterodimer (C5 convertase) formation. Our data provide another explanation for the enhanced serum sensitivity of Por1B-bearing gonococci. The binding of C3b and C4b to Opa provides a rationale for the recovery of predominantly "transparent" (Opa-negative) neisserial isolates from persons with invasive disease, where the bacteria encounter high levels of complement.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17984207&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectBacterial Outer Membrane Proteins
dc.subjectComplement C3b
dc.subjectComplement C4b
dc.subjectHumans
dc.subjectNeisseria gonorrhoeae
dc.subjectNeisseria meningitidis
dc.subjectPorins
dc.subjectProtein Binding
dc.subjectProtein Isoforms
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleDefining targets for complement components C4b and C3b on the pathogenic neisseriae
dc.typeJournal Article
dc.source.journaltitleInfection and immunity
dc.source.volume76
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2261&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1262
dc.identifier.contextkey782929
refterms.dateFOA2022-08-23T16:34:43Z
html.description.abstract<p>Complement is a key arm of the innate immune defenses against the pathogenic neisseriae. We previously identified lipooligosaccharide on Neisseria meningitidis as an acceptor for complement C4b. Little is known about other neisserial targets for complement proteins C3 and C4, which covalently attach to bacterial surfaces and initiate opsonization and killing. In this study we demonstrate that Neisseria gonorrhoeae porin (Por) 1B selectively binds C4b via amide linkages and C3b via ester linkages. Using strains expressing hybrid Por1A/1B molecules, a region spanned by loops 4 and 5 of Por1B was identified as the preferred binding site for C4b. We also identified the opacity protein (Opa), a major adhesin of pathogenic neisseriae, as a target for C4b and C3b on both N. meningitidis and N. gonorrhoeae. Using N. gonorrhoeae variants that predominantly expressed individual Opa proteins, we found that all Opa proteins tested (A, B, C, D, E, F, and I) bound C4b and C3b via amide and ester linkages, respectively. Amide linkages with Por1B and Opa were confirmed using serum containing only the C4A isoform, which exclusively forms amide linkages with targets. While monomers and heterodimers of C4Ab were detected on bacterial targets, C4Bb appeared to preferentially participate in heterodimer (C5 convertase) formation. Our data provide another explanation for the enhanced serum sensitivity of Por1B-bearing gonococci. The binding of C3b and C4b to Opa provides a rationale for the recovery of predominantly "transparent" (Opa-negative) neisserial isolates from persons with invasive disease, where the bacteria encounter high levels of complement.</p>
dc.identifier.submissionpathoapubs/1262
dc.contributor.departmentDivision of Infectious Diseases and Immunology
dc.source.pages339-50


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