Haemophilus influenzae acquires vitronectin via the ubiquitous Protein F to subvert host innate immunity

Mol Microbiol. 2013 Mar;87(6):1245-66. doi: 10.1111/mmi.12164. Epub 2013 Feb 26.


Acquisition of the complement inhibitor vitronectin (Vn) is important for the respiratory tract pathogen nontypeable Haemophilus influenzae (NTHi) to escape complement-mediated killing. NTHi actively recruits Vn, and we previously showed that this interaction involves Protein E (PE). Here we describe a second Vn-binding protein, a 30 kDa Yersinia YfeA homologue designated as Protein F (PF). An isogenic NTHi 3655Δhpf mutant devoid of PF displayed a reduced binding of Vn, and was consequently more sensitive to killing by human serum compared with the wild type. Surface expression of PF on Escherichia coli conferred binding of Vn that resulted in a serum resistant phenotype. Molecular analyses revealed that the N-terminal of PF (Lys23-Glu48) bound to the C-terminal of Vn (Phe352-Ser374) without disrupting the inhibitory role of Vn on the membrane attack complex. The PF-Vn complex actively delayed C9 deposition on PF-expressing bacteria. Comparative studies of binding affinity and multiple mutants demonstrated that both PE and PF contribute individually to NTHi serum survival. PF was highly conserved and ubiquitously expressed in a series of randomly selected NTHi clinical isolates (n = 18). In conclusion, the multifaceted binding of Vn is beneficial for NTHi survival in serum and may contribute to successful colonization and consequently infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Blood Bactericidal Activity
  • Gene Deletion
  • Haemophilus influenzae / genetics
  • Haemophilus influenzae / immunology*
  • Haemophilus influenzae / metabolism*
  • Humans
  • Immune Evasion*
  • Immunity, Innate*
  • Microbial Viability
  • Protein Binding
  • Protein Interaction Mapping
  • Vitronectin / metabolism*


  • Bacterial Proteins
  • Vitronectin