Heptose I glycan substitutions on Neisseria gonorrhoeae lipooligosaccharide influence C4b-binding protein binding and serum resistance
Authors
Ram, SanjayNgampasutadol, Jutamas
Cox, Andrew D.
Blom, Anna M.
Lewis, Lisa A.
St. Michael, Frank
Stupak, Jacek
Gulati, Sunita
Rice, Peter A.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2007-05-29Keywords
Blood Bactericidal ActivityColony Count, Microbial
Complement C4b-Binding Protein
Galactosyltransferases
Heptoses
Humans
Lipopolysaccharides
Mutation
Neisseria gonorrhoeae
Porins
Protein Binding
Serum
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Lipooligosaccharide (LOS) heptose (Hep) glycan substitutions influence gonococcal serum resistance. Several gonococcal strains bind the classical complement pathway inhibitor, C4b-binding protein (C4BP), via their porin (Por) molecule to escape complement-dependent killing by normal human serum (NHS). We show that the proximal glucose (Glc) on HepI is required for C4BP binding to Por1B-bearing gonococcal strains MS11 and 1291 but not to FA19 (Por1A). The presence of only the proximal Glc on HepI (lgtE mutant) permitted maximal C4BP binding to MS11 but not to 1291. Replacing 1291 lgtE Por with MS11 Por increased C4BP binding to levels that paralleled MS11 lgtE, suggesting that replacement of the Por1B molecule dictated the effects of HepI glycans on C4BP binding. The remainder of the strain background did not affect C4BP binding; replacing the Por of strain F62 with MS11 Por (F62 PorMS11) and truncating HepI mirrored the findings in the MS11 background. C4BP binding correlated with resistance to killing by NHS in most instances. F62 PorMS11 and its lgtE mutant were sensitive to NHS despite binding C4BP, secondary to kinetically overwhelming classical pathway activation and possibly increased alternative pathway activation (measured by factor Bb binding) by the F62 background. FA19 lgtF (HepI unsubstituted) resisted killing by only 10% NHS, not 50% NHS, despite binding levels of C4BP similar to those of FA19 and FA19 lgtE (both resistant to 50% serum), suggesting a role for the proximal Glc in serum resistance independently of C4BP binding. This study provides mechanistic insights into how HepI LOS substitutions affect the serum resistance of N. gonorrhoeae.Source
Infect Immun. 2007 Aug;75(8):4071-81. Epub 2007 May 25. Link to article on publisher's siteDOI
10.1128/IAI.01109-06Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38398PubMed ID
17526744Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/IAI.01109-06