The contrasting mechanisms of serum resistance of Neisseria gonorrhoeae and group B Neisseria meningitidis.
Neisseria gonorrhoeae and Neisseria meningitidis have evolved intricate mechanisms to evade complement-mediated killing. Sialylation of gonococcal lipooligosaccharide (LOS) results in conversion of previously serum sensitive strains to unstable serum resistance, which is mediated by factor H binding. Porin (Por) is also instrumental in mediating stable serum resistance in gonococci. The 5th loop of certain gonococcal PorlAs binds factor H, which efficiently inactivates C3b to iC3b. Factor H glycan residues may be essential for factor H binding to certain Por1A strains. Por1A strains can also regulate the classical pathway by binding to C4b-binding protein (C4bp) probably via the 1st loop of the Por molecule. Certain serum resistant Por1 B strains can also regulate complement by binding C4bp through a loop other than loop 1. Purified C4b can inhibit binding of C4bp to Por 1B, but not Por1A, suggesting different binding sites on C4bp for the two Por types. Unlike serum resistant gonococci, resistant meningococci have abundant C3b on their surface, which is only partially processed to iC3b. The main mechanism of complement evasion by group B meningococci is inhibition of membrane attack complex (MAC) insertion by their polysaccharide capsule. LOS structure may act in concert with capsule to prevent MAC insertion. Meningococcal strains with Class 3 Por preferentially bind factor H, suggesting Class 3 Por acts as a receptor for factor H.
Ram
S
S
The Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, MA 02118, USA. sram@bu.edu
Mackinnon
F G
FG
Gulati
S
S
McQuillen
D P
DP
Vogel
U
U
Frosch
M
M
Elkins
C
C
Guttormsen
H K
HK
Wetzler
L M
LM
Oppermann
M
M
Pangburn
M K
MK
Rice
P A
PA
D001770:Blood Bactericidal Activity / Q000276:immunology*; D003165:Complement System Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology; D009344:Neisseria gonorrhoeae / Q000276:immunology* / Q000472:pathogenicity; D009345:Neisseria meningitidis / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity; D018272:Porins / Q000276:immunology; D013045:Species Specificity
D008070:Lipopolysaccharides; D018272:Porins; C023023:lipid-linked oligosaccharides; D003165:Complement System Proteins