Relationship between colony morphology and the life cycle of Haemophilus influenzae: the contribution of lipopolysaccharide phase variation to pathogenesis.

Colonies of Haemophilus influenzae are heterogeneous in appearance because of phase variation in opacity. The only cell surface component found to have structural variation correlating with differences in opacity was the lipopolysaccharide (LPS). Changes in LPS structure, seen as migration patterns on tricine-SDS-PAGE, appeared to be independent of a previously described mechanism for generating LPS phase variation. The more transparent variants expressing a higher-molecular-weight LPS were serum sensitive and could efficiently colonize the infant rat nasopharynx after intranasal inoculation. In contrast, the fully opaque variant expressing a smaller-molecular-weight LPS was serum resistant, unable to colonize the nasopharynx, and more virulent when intraperitoneally administered. Organisms disseminating into the blood-stream from the nasopharynx changed phenotype from transparent to opaque. These findings demonstrate the potential importance of LPS structures that determine opacity in pathogenesis and colonization of mucosal surfaces.