Salmonella and Complement: The Critical Influence of O-Polysaccharide within LPS

Abstract

Virulent enteric gram negative bacteria generally produce lipopolysaccharide molecules bearing O-antigen side chains. This scenario applies despite the fact that nearly all of the in vitro and in vivo toxic effects of LPS are ascribed to the lipid A portion of the molecule. Thus, there is an apparent survival advantage to the organism in producing LPS with O-polysaccharide side chains. Although the presence of O-polysaccharide confers some advantage to the cell in fending off harmful exogenous hydrophobic molecules, the overall fluidity and permeability of the outer membrane is not altered substantially merely as a consequence of O-antigen addition (1). Certainly, one survival advantage to cells bearing O-antigen resides in their capacity to evade the host humoral immune system. The presence within virulent organisms of O-antigen serotypes not commonly encountered insures that the native host will not have developed specific antibody to the organism at the time of invasion. A second factor, and the subject of this paper, is that O-antigen within LPS is the major determinant influencing the interaction of the complement system with the gram negative cell wall. In fact, it could be argued that this is the most clearly demonstrated consequence of O-antigen within LPS. The theme of this manuscript is that both the carbohydrate composition of the O-antigen, which dictates the extent of opsonic C3 fragment deposition by the alternative complement pathway, and the size and distribution of O-antigen, which determines the susceptibility to direct killing by the alternative complement pathway, are major virulence determinants for LPS within enteric organisms.