Arthropathic properties of gonococcal peptidoglycan fragments: implications for the pathogenesis of disseminated gonococcal disease

Abstract

We examined the arthropathic activity of purified peptidoglycan (PG) fragments derived from (i) lysozyme-resistant, extensively O-acetylated PG from Neisseria gonorrhoeae FA19 (O-PG), and (ii) lysozyme-sensitive, O-acetyl-deficient PG from N. gonorrhoeae RD5 (non-O-PG). Male Lewis rats were injected intradermally in the tail with 200 micrograms of PG emulsified in mineral oil and water (1:1) or with the oil and water emulsion alone (controls). Quantitation of hind paw size indicated that macromolecular PG of various chemical and physical forms induced paw swelling (P versus controls, less than 0.01) that was evident at about day 14 and that reached a maximum at about day 24. PG-mediated paw swelling was accompanied by intense synovitis with some cartilage and bone involvement. The minimal arthropathic dose of soluble macromolecular PG was 20 micrograms per rat. Of particular interest was that macromolecular O-PGs from strain FA19 caused considerably more extensive swelling than did either their RD5 non-O-PG counterparts or the homologous FA19 PG that had been de-O-acetylated by mild alkali treatment. This suggested that the persistence of hydrolase-resistant high-molecular-weight fragments, afforded by extensive O-acetylation, may be important for optimal expression of arthropathic activity. However, oligomeric PG was not an absolute requirement, since even low-molecular-weight fragments, including the anhydro-muramyl-containing disaccharide peptide monomer released by growing gonococci, were also arthritogenic. Experiments employing purified gonococcal lipopolysaccharide indicated that the arthropathic activity of PG preparations was not due to contaminating lipopolysaccharide. Based on the arthritogenicity of gonococcal PG in this model system, we suggest that PG may play a role in the pathogenesis of gonococcal arthritis, and that such an activity might be potentiated by the persistence of hydrolase-resistant O-PG.