Haemophilus influenzae protein E binds to the extracellular matrix by concurrently interacting with laminin and vitronectin

J Infect Dis. 2011 Oct 1;204(7):1065-74. doi: 10.1093/infdis/jir459.

Abstract

Nontypeable Haemophilus influenzae (NTHi) causes otitis media and is commonly found in patients with chronic obstructive pulmonary disease (COPD). Adhesins are important for bacterial attachment and colonization. Protein E (PE) is a recently characterized ubiquitous 16 kDa adhesin with vitronectin-binding capacity that results in increased survival in serum. In addition to PE, NTHi utilizes Haemophilus adhesion protein (Hap) that binds to the basement-membrane glycoprotein laminin. We show that most clinical isolates bind laminin and that both Hap and PE are crucial for the NTHi-dependent interaction with laminin as revealed with different mutants. The laminin-binding region is located at the N-terminus of PE, and PE binds to the heparin-binding C-terminal globular domain of laminin. PE simultaneously attracts vitronectin and laminin at separate binding sites, proving the multifunctional nature of the adhesin. This previously unknown PE-dependent interaction with laminin may contribute to NTHi colonization, particularly in smokers with COPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / chemistry*
  • Adhesins, Bacterial / physiology
  • Adult
  • Aged
  • Aged, 80 and over
  • Binding Sites
  • Child
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix / chemistry*
  • Female
  • Fibrinogen / chemistry
  • Fibronectins / chemistry
  • Haemophilus influenzae / metabolism*
  • Haemophilus influenzae / physiology
  • Humans
  • Infant
  • Laminin / chemistry*
  • Male
  • Middle Aged
  • Surface Plasmon Resonance
  • Vitronectin / chemistry*
  • Young Adult

Substances

  • Adhesins, Bacterial
  • Fibronectins
  • Laminin
  • Vitronectin
  • Fibrinogen