The possession of type b capsule has been shown to be a major virulence factor in Haemophilus influenzae. Animal studies of isogenic strains transformed with capsule associated DNA confirmed earlier observations that type b strains were more virulent than type a strains, which were more virulent than the other capsular types (Zwahlen et al., 1989). The bacterial capsule aids colonisation and is probably the most important virulence factor for invasive disease, as it protects against phagocytosis and complement-mediated lysis (Moxon et al., 1990, Tunkel et al., 1993).

Endotoxin or its subcomponent lipooligosaccharide (LOS) has been suggested as an important virulence factor for H. influenzae (Makela et al., 1988). H. influenzae LOS is analogous to the lipopolysaccharide (LPS) of enteric gram-negative bacteria in that it contains lipid A linked by 3-deoxy-D-manno- octulosonic acid (KDO) to a heterogeneous sugar polymer (Gibson et al., 1993). Haemophilus LOS, however, differs from classic enterobacterial LPS in that it does not contain repeating O-antigen units . Endotoxin is present in the bacterial outer membrane but is also released in a biologically active form during growth or as a result of antibiotic- or immune response-mediated death of the organism (Gu et al., 1995, Mandrell et al., 1992). Endotoxin is a potent, biologically active mediator known to effect the release of various vasoactive amines and other mediators of inflammation by direct interaction with macrophages, polymorphonuclear neutrophils, and other cell types (DeMaria et al., 1997, Valvano, 1992).

Hemagglutinating pili are peritrichous, hair-like polymeric structures that protrude from the H. influenzae outer membrane (Gilsdorf et al., 1997, Stull et al., 1984) and mediate adherence to sialic acid-containing lactosylceramide structures on epithelial cell surfaces (Van Alphen et al., 1991). Biosynthesis of pili requires the products of five genes, hifA through hifE, located in the pilus gene hif cluster (Gilsdorf et al., 1997, Watson et al., 1994). Bacterial expression of hemagglutinating pili is altered through a process called phase variation, which is mediated by slipped-strand mispairing (Gilsdorf et al., 1997), suggesting a means by which H. influenzae may rapidly adapt to changing environments. By extension, this also suggests that the presence or absence of the pilus gene cluster is important to H. influenzae in its adaptation to the environment (Moxon et al., 1994).