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Factor H Binding and Function in Sialylated Pathogenic Neisseriae is Influenced by Gonococcal, but Not Meningococcal, Porin¹

Guillermo Madico^*, Jutamas Ngampasutadol, Sunita Gulati, Ulrich Vogel, Peter A. Rice and Sanjay Ram^2,

^* Evans Biomedical Research Center, Boston University Medical Center, Boston, MA 02118; Division of Infectious Diseases and Immunology, University of Massachusetts Memorial Medical Center, Worcester, MA 01605; and Institute for Hygiene and Microbiology, Universität Würzburg, 97080 Würzburg, Germany

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 µg/ml) concentrations of factor H and decreased in a dose-responsive manner by 80% at 1.25 µg/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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI32725 (to P.A.R.) and AI054544 (to S.R.).

² Address correspondence and reprint requests to Dr. Sanjay Ram, Division of Infectious Diseases and Immunology, University of Massachusetts Memorial Medical Center, Lazare Research Building, Room 322, 364 Plantation Street, Worcester, MA 01605. E-mail address: sanjay.ram{at}umassmed.edu

³ Abbreviations used in this paper: LNT, lacto-N-neotetraose; LOS, lipooligosaccharide; lst, LOS sialyltransferase; NANA, N-acetylneuraminic acid; Gal, galactose; Glc, glucose; GlcNAc, N-acetylglucosamine; Hep, heptose; NHS, normal human serum; PEA, phosphoethanolamine; Por, porin.

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