Elaboration of a 3.6-kilodalton lipooligosaccharide, antibody against which is absent from human sera, is associated with serum resistance of Neisseria gonorrhoeae

Abstract

Neisseria gonorrhoeae strains that resist lysis by normal human sera (NHS) do so, in part, because NHS contain immunoglobulin M (IgM) specific for lipooligosaccharide (LOS) antigens of serum-sensitive strains, but lack antibodies for LOS antigens that can serve as loci for immune lysis of serum-resistant (serr) strains. We used a monoclonal antibody (McAb), specific for an epitope within a 3.6-kilodalton (kDa) component of Neisseria meningitidis L8 LOS, that binds a 3.6-kDa gonococcal LOS component so that we could explore further serr gonococcal strains. The McAb bound to the LOS of 6 of 7 serr of strains but not to the LOS of 0 of 14 serum-sensitive and serum-intermediate gonococcal strains of diverse origin. We studied three serr strains further. Strain 7134 does not elaborate the 3.6-kDa LOS component and does not bind the McAb; strains WR220 and WR302 do elaborate the 3.6-kDa LOS component. The titer (log2) at which the McAb, diluted in NHS, lysed strain WR220 was 7.7; for WR302 it was 3.7, and for 7134 it was 0. Addition of McAb to NHS caused increased classical and alternative-pathway C3 deposition onto strain WR220, but only classicalpathway-activated C3 deposition onto strain WR302. The difference in lytic effectiveness of the McAb for the two strains, therefore, may result from differences in alternative-pathway augmentation of McAb-dependent classical-pathway activation on their surfaces. None of 40 randomly selected normal young adults had serum antibody that could compete with the McAb for binding to WR220 LOS in a solid-phase RIA. We conclude that the 3.6-kDa LOS component is commonly expressed by serr strains of N. gonorrhoeae and that antibody to it would be lytic if present in human serum, but that it is infrequently, if ever, present. As a result, strains elaborating this LOS are resistant to lysis by NHS.

Binding of C4b-Binding Protein to Porin

“…5). These data provide evidence that, in addition to binding C4bp, the Por molecule may also dictate levels of IgM binding to surface targets, most likely LOS 156061. In addition, levels of C3 and C5b-9 binding to F62 PorMS11 were greater than for F62 loop1 MS11 loop2–8 , but less so than for F62 (Fig.…”

“…Disseminated bloodstream infection with gonococci (DGI) often occurs in the absence of local genital inflammation and is caused predominantly by gonococci that resist killing by NHS independent of sialylation, termed stable serum resistance 14. These isolates sometimes lack the LOS acceptor site for sialic acid 15, or may not completely sialylate LOS for reasons that remain unclear. Commonly they also express the gonococcal major outer membrane protein serotype porin (Por)1A 1617.…”

Genetic locus for the biosynthesis of the variable portion of Neisseria gonorrhoeae lipooligosaccharide.

“…Similarly, a change in lgtA would cause the failure of the addition of GlcNAc to the growing chain and truncate the LOS at the 13-1actosyl level. This is a very common form of LOS in gonococci, with a 3.6-kD molecule that confers resistance to the bactericidal effect of normal human serum (71). It is tempting to speculate that the in vitro variation between variants A and C of MSllmk from the fl-lactosyl chain to a complete LOS (which had a selective advantage in vivo in the volunteers) could be explained by regaining functional expression of the influenzae LOS has also been noted and has been attributed to changes in translational frame caused by shifts in the number of CAAT repeats in two separate loci, licl (72) and lic2 (62).…”

Characterization of fourteen strains of Neisseria gonorrhoeae: structural analyses and serum reactivities

“…TLE, thin-layer electrophoresis; TLC, thin-layer chromatography. SR gonococcal strains, and NHS rarely contains Ab to it (Schneider et aL, 1985;Stephens and Shafer, 1987), However, the 3.6 kD epitope is only one of several LPS components expressed by SR strains; some SR strains do not express it, others express very little, and some L8-transformants remain SS {Schneider etai, 1985;Stein ef aL, 1988), The availability of transformant strains with identical Pis in various LPS backgrounds facilitated our study of the role of LPS in serum killing. For these nine strains we found a perfect correlation between LPS types and serum reactivities; all sensitive strains had 'deep rough'-type LPS, and all resistant strains had 'rough'-type LPS, However, the relationship did not hold for all of the other five strains.…”