Complement activation by Proteus mirabilis negatively charged lipopolysaccharides

Proteus mirabilis strains are human pathogens responsible for urinary tract infections and bacteremias and may be involved in rheumatoid arthritis. Li popolysaccharide (LPS,bacterial endotoxin), the major component of the cell wall, is one of the virulence factors of Proteus. In the presented studies , we have investigated complement activation by LPSs isolated from P. mirab ilis O10, O23, O30, and O43 strains, which differ in the number of negative COO- groups on their polysaccharide components. Four P. mirabilis strains studied were sensitive to complement-mediated killing, despite complement b inding by their LPSs. The optimal complement binding by LPSs was detected i n serum with functional assays for both the classical and alternative pathw ays. Complement activation in 80% serum by the smooth, uronic acid, and hexosami ne containing P. mirabilis LPSs was not critically determined by the struct ure of their O-chain polysaccharides. One of four LPSs used as a model, P. mirabilis O10 LPS, fragmented C3 in an LPS dose- and time-dependent manner. It was detected by crossed-immunoelectrophoresis and capture ELISA with an ti-C3c antibodies. The lower complement activation by O23 LPS correlates wi th its reduced C3 fragmentation, compared with three other Proteus LPSs stu died. Rabbit anti-O antibodies enhanced the complement binding and factor C 3 fragmentation by O10, O23, O30, and O43 P. mirabilis LPSs.