Loss of capsule expression by Haemophilus influenzae type b results in enhanced adherence to and invasion of human cells

Abstract

Haemophilus influenzae type b is a common cause of systemic bacterial disease in children, and the serotype b capsule is a major determinant of virulence. Nevertheless, as a consequence of the genetic configuration of the capb locus, type b strains become capsule deficient at a high frequency. To investigate the potential biological relevance of the predisposition to capsule loss, we compared the adherent and invasive abilities of several strains of H. influenzae type b and their isogenic capsule-deficient mutants by using cultured human epithelial cells. In all cases the capsule-deficient mutant demonstrated significantly greater adherence and invasion than the encapsulated parent. Transformation of one capsule-deficient mutant to restore encapsulation resulted in a marked decrease in adherence and invasion. All strains were capable of adherence and invasion by a pilus-independent mechanism. We conclude that capsule loss by H. influenzae type b results in enhanced in vitro adherence and invasion, properties that may be relevant to colonization of the nasopharynx and persistence within the respiratory tract. These observations suggest an explanation for the evolution of the capb locus as directly repeated segments of DNA with a consequent predisposition to recombination resulting in capsule loss.