Contribution of lipopolysaccharide to pathogenicity of Haemophilus influenzae: comparative virulence of genetically-related strains in rats

Abstract

The elaboration of type b capsule plays an important role in determining virulence of Haemophilus influenzae but the contribution of lipopolysaccharide to pathogenicity of this organism remains undefined. Using DNA from a virulent type b H. influenzae donor strain and a capsule-deficient recipient (Rd:01), we constructed capsular transformants having lipopolysaccharide characteristics either similar to (strain Rd/b+:01), or different from (strain Rd/b+:02), the recipient strain. These two type b transformants had similar type b capsule and outer membrane proteins. Comparative virulence studies in rats showed that strain Rd/b+:02 was more virulent than Rd/b+01 as assessed by magnitude of bacteraemia, incidence of meningitis and mortality. Similarly, strain Rd/b-:02 exhibited greater pathogenicity in C3-depleted rats than its genetically-related strain Rd:01. We conclude that lipopolysaccharide composition plays a significant role in mediating the potential of H. influenzae to cause invasive infections. In addition, the findings suggest that there is linkage of virulence genes involved in lipopolysaccharide and capsule expression.