Haemophilus influenzae Protein F Mediates Binding to Laminin and Human Pulmonary Epithelial Cells.

The mucosal pathogen non-typeable Haemophilus influenzae (NTHi) adheres to the respiratory epithelium, or in the case of epithelial damage, to the underlying basement membrane and extracellular matrix that amongst other proteins consists of laminin. We have recently identified Protein F, an ABC-transporter involved in NTHi immune evasion. Homology modeling of the Protein F tertiary structure revealed a strong resemblance to the streptococcal laminin-binding proteins Lbp and Lmb. Here, we show that Protein F promotes binding of NTHi to laminin and primary bronchial epithelial cells. Analyses with recombinant proteins and synthetic peptides revealed that the N-terminal part of Protein F contains the host-interacting region. Moreover, Protein F exists in all clinical isolates, and isogenic NTHi Δhpf mutants display significantly reduced binding to laminin and epithelial cells. We thus suggest Protein F as an important and ubiquitous NTHi adhesin.