This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shaughnessy, J. Articles by Ram, S. Search for Related Content PubMed PubMed Citation Articles by Shaughnessy, J. Articles by Ram, S.

 Previous Article  |  Next Article 

Infection and Immunity, May 2009, p. 2094-2103, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01561-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Functional Comparison of the Binding of Factor H Short Consensus Repeat 6 (SCR 6) to Factor H Binding Protein from Neisseria meningitidis and the Binding of Factor H SCR 18 to 20 to Neisseria gonorrhoeae Porin ^,

Jutamas Shaughnessy,^1, Lisa A. Lewis,^1*, Hanna Jarva,² and Sanjay Ram¹

Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605,¹ Haartman Institute, Department of Bacteriology and Immunology, University of Helsinki, 00014 Helsinki, Finland²

Received 23 December 2008/ Returned for modification 3 February 2009/ Accepted 26 February 2009

Both Neisseria meningitidis and Neisseria gonorrhoeae recruit the alternative pathway complement inhibitory protein factor H (fH) to their surfaces to evade complement-dependent killing. Meningococci bind fH via fH binding protein (fHbp), a surface-exposed lipoprotein that is subdivided into three variant families based on one classification scheme. Chimeric proteins that comprise contiguous domains of fH fused to murine Fc were used to localize the binding site for all three fHbp variants on fH to short consensus repeat 6 (SCR 6). As expected, fH-like protein 1 (FHL-1), which contains fH SCR 6, also bound to fHbp-expressing meningococci. Using site-directed mutagenesis, we identified histidine 337 and histidine 371 in SCR 6 as important for binding to fHbp. These findings may provide the molecular basis for recent observations that demonstrated human-specific fH binding to meningococci. Differences in the interactions of fHbp variants with SCR 6 were evident. Gonococci bind fH via their porin (Por) molecules (PorB.1A or PorB.1B); sialylation of lipooligosaccharide enhances fH binding. Both sialylated PorB.1B- and (unsialylated) PorB.1A-bearing gonococci bind fH through SCR 18 to 20; PorB.1A can also bind SCR 6, but only weakly, as evidenced by a low level of binding of FHL-1 relative to that of fH. Using isogenic strains expressing either meningococcal fHbp or gonococcal PorB.1B, we discovered that strains expressing gonococcal PorB.1B in the presence of sialylated lipooligosaccharide bound more fH, more effectively limited C3 deposition, and were more serum resistant than their isogenic counterparts expressing fHbp. Differences in fH binding to these two related pathogens may be important for modulating their individual responses to host immune attack.

---

* Corresponding author. Mailing address: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Lazare Research Building, Room 370I, Plantation Street, Worcester, MA 01605. Phone: (508) 856-587. Fax: (508) 856-5463. E-mail: lisa.lewis{at}umassmed.edu

Published ahead of print on 9 March 2009.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. N. Weiser

These authors contributed equally to this work.

---

Infection and Immunity, May 2009, p. 2094-2103, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01561-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.