The Haemophilus influenzae Hap serine protease promotes adherence and microcolony formation, potentiated by a soluble host protein

Mol Cell. 1998 Dec;2(6):841-50. doi: 10.1016/s1097-2765(00)80298-1.

Abstract

Haemophilus influenzae initiates infection by colonizing the upper respiratory mucosa. The process of colonization involves adherence to epithelium and evasion of host immunity. In this study, we examined the H. influenzae Hap adhesin, which has serine protease activity and undergoes autoproteolytic cleavage and extracellular release in broth. We found that the uncleaved cell-associated form of Hap mediates adherence to cultured epithelial cells and promotes bacterial aggregation and microcolony formation. Adherence and aggregation are augmented by secretory leukocyte protease inhibitor, a natural component of respiratory secretions that inhibits Hap autoproteolysis. These observations suggest a novel paradigm in host-pathogen relations, in which a soluble host protein whose primary function is to protect host epithelium potentiates properties that facilitate bacterial colonization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Adhesion / physiology*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacterial Outer Membrane Proteins / physiology*
  • Binding Sites
  • Colony Count, Microbial
  • Haemophilus influenzae / enzymology*
  • Haemophilus influenzae / growth & development
  • Haemophilus influenzae / pathogenicity
  • Humans
  • Hydrolysis
  • Microscopy, Electron, Scanning
  • Mutation
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins / physiology*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Serine Endopeptidases / physiology*
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / microbiology

Substances

  • Bacterial Outer Membrane Proteins
  • Hap protein, Hemophilus influenzae
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins
  • Serine Endopeptidases