Enhanced factor H binding to sialylated Gonococci is restricted to the sialylated lacto-N-neotetraose lipooligosaccharide species: implications for serum resistance and evidence for a bifunctional lipooligosaccharide sialyltransferase in Gonococci
Authors
Gulati, SunitaCox, Andrew D.
Lewis, Lisa A.
St. Michael, Frank
Li, Jianjun
Boden, Ryan
Ram, Sanjay
Rice, Peter A.
UMass Chan Affiliations
Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2005-10-22Keywords
Amino Acid SequenceComplement Factor H
Female
Humans
Immune Sera
Lipopolysaccharides
Male
Molecular Sequence Data
Mutation
N-Acetylneuraminic Acid
Neisseria gonorrhoeae
Oligosaccharides
Protein Binding
Sequence Homology, Amino Acid
Sialyltransferases
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
We isolated serologically identical (by serovar determination and porin variable region [VR] typing) strains of Neisseria gonorrhoeae from an infected male and two of his monogamous female sex partners. One strain (termed 398078) expressed the L1 (Galalpha1 --> 4 [corrected] Galbeta1 --> 4Glcbeta1 --> 4HepI) lipooligosaccharide (LOS) structure exclusively; the other (termed 398079) expressed the lacto-N-neotetraose (LNT; Galbeta1 --> 4GlcNAcbeta1 --> 3Galbeta1 --> 4Glcbeta1 --> 4HepI) LOS structure. The strain from the male index case expressed both glycoforms and exhibited both immunotypes. Nuclear magnetic resonance analysis revealed that sialic acid linked to the terminal Gal of L1 LOS via an alpha2 --> 6 linkage and, as expected, to the terminal Gal of LNT LOS via an alpha2--> 3 linkage. Insertional inactivation of the sialyltransferase gene (known to sialylate LNT LOS) abrogated both L1 LOS sialylation and LNT LOS sialylation, suggesting a bifunctional nature of this enzyme in gonococci. Akin to our previous observations, sialylation of the LNT LOS of strain 398079 enhanced the binding of the complement regulatory molecule, factor H. Rather surprisingly, factor H did not bind to sialylated strain 398078. LOS sialylation conferred the LNT LOS-bearing strain complete (100%) resistance to killing by even 50% nonimmune normal human serum (NHS), whereas sialylation of L1 LOS conferred resistance only to 10% NHS. The ability of gonococcal sialylated LNT to bind factor H confers high-level serum resistance, which is not seen with sialylated L1 LOS. Thus, serum resistance mediated by sialylation of gonococcal L1 and LNT LOS occurs by different mechanisms, and specificity of factor H binding to sialylated gonococci is restricted to the LNT LOS species.Source
Infect Immun. 2005 Nov;73(11):7390-7. Link to article on publisher's siteDOI
10.1128/IAI.73.11.7390-7397.2005Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42263PubMed ID
16239538Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/IAI.73.11.7390-7397.2005