Haemophilus influenzae protein F mediates binding to laminin and human pulmonary epithelial cells

Area of Science:

• Microbiology
• Immunology
• Structural Biology

Background:

• Nontypeable Haemophilus influenzae (NTHi) is a mucosal pathogen that colonizes the respiratory tract.
• NTHi adherence to respiratory epithelium or extracellular matrix components like laminin is critical for infection.
• Protein F, an ABC transporter, was recently identified as a factor in NTHi immune evasion.

Purpose of the Study:

• To investigate the role of NTHi protein F in binding to host cells and laminin.
• To identify the host-interacting region of protein F.
• To determine the prevalence and significance of protein F in clinical NTHi isolates.

Main Methods:

• Homology modeling of protein F structure.
• Binding assays using recombinant protein F, synthetic peptides, NTHi strains, laminin, and primary bronchial epithelial cells.
• Analysis of isogenic NTHi Δhpf mutants.

Main Results:

• Protein F shares structural similarity with streptococcal laminin-binding proteins.
• Protein F mediates the binding of NTHi to laminin and bronchial epithelial cells.
• The N-terminal region of protein F is responsible for host cell interaction.
• Protein F is present in all tested clinical NTHi isolates.
• NTHi mutants lacking protein F (Δhpf) showed significantly reduced binding to laminin and epithelial cells.

Conclusions:

• Protein F is a significant adhesin for nontypeable Haemophilus influenzae.
• Protein F facilitates NTHi's interaction with the respiratory epithelium via laminin binding.
• Protein F is a ubiquitous and important virulence factor in NTHi infections.