%0 Journal Article %1 madico_factor_2007 %A Madico, Guillermo %A Ngampasutadol, Jutamas %A Gulati, Sunita %A Vogel, Ulrich %A Rice, Peter A %A Ram, Sanjay %D 2007 %J Journal of Immunology (Baltimore, Md.: 1950) %K Acid, Alleles, Complement Factor H, Humans, Mutation, Neisseria Oligosaccharides, Porins, gonorrhoeae, meningitidis, serum_resistance {N-Acetylneuraminic}, %N 7 %P 4489--4497 %T Factor H binding and function in sialylated pathogenic neisseriae is influenced by gonococcal, but not meningococcal, porin %U http://www.ncbi.nlm.nih.gov/pubmed/17372007 %V 178 %X Neisseria gonorrhoeae and Neisseria meningitidis both express the lacto-N-neotetraose (LNT) lipooligosaccharide (LOS) molecule that can be sialylated. Although gonococcal LNT LOS sialylation enhances binding of the alternative pathway complement inhibitor factor H and renders otherwise serum-sensitive bacteria resistant to complement-dependent killing, the role of LOS sialylation in meningococcal serum resistance is less clear. We show that only gonococcal, but not meningococcal, LNT LOS sialylation enhanced factor H binding. Replacing the porin (Por) B molecule of a meningococcal strain (LOS sialylated) that did not bind factor H with gonococcal Por1B augmented factor H binding. Capsule expression did not alter factor H binding to meningococci that express gonococcal Por. Conversely, replacing gonococcal Por1B with meningococcal PorB abrogated factor H binding despite LNT LOS sialylation. Gonococcal Por1B introduced in the background of an unsialylated meningococcus itself bound small amounts of factor H, suggesting a direct factor H-Por1B interaction. Factor H binding to unsialylated meningococci transfected with gonococcal Por1B was similar to the sialylated counterpart only in the presence of higher (20 microg/ml) concentrations of factor H and decreased in a dose-responsive manner by approximately 80\% at 1.25 microg/ml. Factor H binding to the sialylated strain remained unchanged over this factor H concentration range however, suggesting that LOS sialylation facilitated optimal factor H-Por1B interactions. The functional counterpart of factor H binding showed that sialylated meningococcal mutants that possessed gonococcal Por1B were resistant to complement-mediated killing by normal human serum. Our data highlight the different mechanisms used by these two related species to evade complement.

@article{madico_factor_2007, abstract = {Neisseria gonorrhoeae and Neisseria meningitidis both express the {lacto-N-neotetraose} {(LNT)} lipooligosaccharide {(LOS)} molecule that can be sialylated. Although gonococcal {LNT} {LOS} sialylation enhances binding of the alternative pathway complement inhibitor factor H and renders otherwise serum-sensitive bacteria resistant to complement-dependent killing, the role of {LOS} sialylation in meningococcal serum resistance is less clear. We show that only gonococcal, but not meningococcal, {LNT} {LOS} sialylation enhanced factor H binding. Replacing the porin {(Por)} B molecule of a meningococcal strain {(LOS} sialylated) that did not bind factor H with gonococcal {Por1B} augmented factor H binding. Capsule expression did not alter factor H binding to meningococci that express gonococcal Por. Conversely, replacing gonococcal {Por1B} with meningococcal {PorB} abrogated factor H binding despite {LNT} {LOS} sialylation. Gonococcal {Por1B} introduced in the background of an unsialylated meningococcus itself bound small amounts of factor H, suggesting a direct factor {H-Por1B} interaction. Factor H binding to unsialylated meningococci transfected with gonococcal {Por1B} was similar to the sialylated counterpart only in the presence of higher (20 microg/ml) concentrations of factor H and decreased in a dose-responsive manner by approximately 80\% at 1.25 microg/ml. Factor H binding to the sialylated strain remained unchanged over this factor H concentration range however, suggesting that {LOS} sialylation facilitated optimal factor {H-Por1B} interactions. The functional counterpart of factor H binding showed that sialylated meningococcal mutants that possessed gonococcal {Por1B} were resistant to complement-mediated killing by normal human serum. Our data highlight the different mechanisms used by these two related species to evade complement.}, added-at = {2011-06-24T11:21:47.000+0200}, author = {Madico, Guillermo and Ngampasutadol, Jutamas and Gulati, Sunita and Vogel, Ulrich and Rice, Peter A and Ram, Sanjay}, biburl = {https://www.bibsonomy.org/bibtex/2e92c43ff2b958e024f89c9db348fa14b/ag_vogel}, interhash = {b74051f05cfdd635919d7d542954550d}, intrahash = {e92c43ff2b958e024f89c9db348fa14b}, issn = {0022-1767}, journal = {Journal of Immunology {(Baltimore}, Md.: 1950)}, keywords = {Acid, Alleles, Complement Factor H, Humans, Mutation, Neisseria Oligosaccharides, Porins, gonorrhoeae, meningitidis, serum_resistance {N-Acetylneuraminic},}, month = apr, note = {{PMID:} 17372007}, number = 7, pages = {4489--4497}, timestamp = {2011-06-24T16:17:33.000+0200}, title = {Factor H binding and function in sialylated pathogenic neisseriae is influenced by gonococcal, but not meningococcal, porin}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17372007}, volume = 178, year = 2007 }