We studied the lipooligosaccharides (LOS) of 28 group A Neisseria meningitidis of epidemiologically diverse origins to investigate whether each of the LOS serotypes found in serogroup A could be identified physically as well as antigenically. Using a dot blot assay with LOS-specific monoclonal antibodies (MAbs), we identified four epitopes that were serotype specific. The LOS from strains of each serotype were electromorphically and antigenically distinct when analyzed by silver-stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. The LOS of L8 strains contained a 3,600-Mr component that bound the L8 MAb. The LOS of L9 strains contained two major components of 4,500 and 4,200 Mr. They bound the L9 MAb to the larger component. The LOS of L10 strains had a single major component of 4,000 Mr that bound the L10 MAb. The LOS of L1l strains contained a major 3,600-Mr component that could not be distinguished from the 3,600-Mr LOS of L8 strains by SDS-PAGE but that bound the Lll MAb. LOS of group A strains contained a highly conserved epitope in addition to a serotype-specific epitope. This was identified by a MAb that bound to all the strains on dot-blots and to multiple LOS components of various Mrs on immunoblots. We conclude that the LOS which bear the L9, L10, and Lll determinants are physically distinct and can be identified by SDS-PAGE or MAb binding or both. L8 and Lll are both borne on a 3.6-kilodalton LOS and can only be distinguished serologically.

Neisseria lactamica, a common human pharyngeal commensal, contributes to acquired immunity to Neisseria meningitidis. To define the surface antigens shared between these two species, we used monoclonal antibodies (MAbs) to study 35 N. lactamica strains isolated in various parts of the world for cross-reactivity with meningococcal capsules, outer membrane proteins, and lipooligosaccharides (LOS). No N. lactamica strain reacted significantly with MAbs specific for capsular group A, B, C, Y, or W, and we were unable to extract capsular polysaccharide from them. Only 2 of 33 strains reacted weakly with MAbs against class 2 serotype proteins P2b and P2c. None reacted with MAbs specific for meningococcal class 1 protein P1.2 or P1.16 or class 2/3 serotype protein P2a or P15. Most N. lactamica strains (30 of 35) bound one or more of seven LOS-specific MAbs. Two LOS epitopes, defined by MAbs 06B4 and 3F11, that are commonly found on pathogenic Neisseria species were found on 25 of 35 N. lactamica. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting showed that the LOS of N. lactamica are composed of multiple components that are physically and antigenically similar to the LOS of pathogenic Neisseria species. Among four other commensal neisserial species, only Neisseria cinerea shared LOS epitopes defined by MAbs 06B4 and 3F11. Previous studies have shown that pharyngeal colonization with N. lactamica induces bactericidal antibodies against the meningococcus. We postulate that shared N. lactamica and meningococcal LOS epitopes may play an important role in the development of natural immunity to the meningococcus.

Serum-sensitive Neisseria gonorrhoeae strains become serum resistant when grown in the presence of a sialic acid precursor, cytidine monophospho-N-acetylneuraminic acid. We examined the abilities of human neutrophils to phagocytose sialylated and nonsialylated gonococci and observed a decrease in the complementdependent phagocytosis of sialylated gonococci compared with that of nonsialylated gonococci (50.7 versus 25.9%o survival at 30 min). This decrease in opsonophagocytosis after sialylation may contribute to the pathogenicity of gonococcal infections. An acute symptomatic infection with Neisseria gonorrhoeae is characterized by a purulent inflammatory exudate. Smith et al. have shown that cytidine monophospho-Nacetylneuraminic acid (CMP-NANA), a compound present in human serum, secretions, leukocytes, and erythrocytes, can alter gonococci and cause them to become resistant to killing by normal human serum (NHS) when organisms are grown in the presence of this substance (11, 12). The surface glycolipids or lipooligosaccharides (LOS) of gonococci grown in CMP-NANA show a change in their electrophoretic mobilities (12). Our laboratory has shown previously that when gonococci are grown in the presence of CMP-NANA, a 4.5-kDa LOS that bears the terminal carbohydrate structure Galp1->4GlcNAcIl1-*3GalIl1-4Glc (lacto-N

Structural studies indicate that the neisserial lipooligosaccharides (LOS) are composed of an oligosaccharide (OS) portion with a phosphorylated diheptose (Hep) core attached to the toxic lipid A moiety. A conserved meningococcal LOS epitope, defined by monoclonal antibody (MAb) D6A, is expressed on group A and many group B and C meningococci of different LOS serotypes (

The outer membrane glycolipids of Neisseria lack long polysaccharides and are properly termed lipooligosaccharides (LOS). A Neisseria strain makes from two to six LOS of Mr 3150-7100. Different species commonly make LOS of identical Mr and epitope content. Oligosaccharide (OS) differences account for physical heterogeneity. OS consist of a conserved triantenary basal oligosaccharide, two linear segments of (n) hexose residues that determine OS mass, and terminal sequences similar to those of glycosphyngolipids. Epitope expression is linked to physical heterogeneity and conditioned by the molecular environment of the outer membrane. Serotype epitopes are expressed on Mr-restricted LOS. LOS regulate complement activation onto the bacterial surface and, hence, immune lysis.