Haemophilus influenzae P4 Interacts With Extracellular Matrix Proteins Promoting Adhesion and Serum Resistance

J Infect Dis. 2016 Jan 15;213(2):314-23. doi: 10.1093/infdis/jiv374. Epub 2015 Jul 7.


Interaction with the extracellular matrix (ECM) is one of the successful colonization strategies employed by nontypeable Haemophilus influenzae (NTHi). Here we identified Haemophilus lipoprotein e (P4) as a receptor for ECM proteins. Purified recombinant P4 displayed a high binding affinity for laminin (Kd = 9.26 nM) and fibronectin (Kd = 10.19 nM), but slightly less to vitronectin (Kd = 16.51 nM). A P4-deficient NTHi mutant showed a significantly decreased binding to these ECM components. Vitronectin acquisition conferred serum resistance to both P4-expressing NTHi and Escherichia coli transformants. P4-mediated bacterial adherence to pharynx, type II alveolar, and bronchial epithelial cells was mainly attributed to fibronectin. Importantly, a significantly reduced bacterial infection was observed in the middle ear of the Junbo mouse model when NTHi was devoid of P4. In conclusion, our data provide new insight into the role of P4 as an important factor for Haemophilus colonization and subsequent respiratory tract infection.

Keywords: Haemophilus influenzae; adhesion; epithelial cells; extracellular matrix; fibronectin; laminin; serum resistance; vitronectin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Adhesion / physiology*
  • Bacterial Outer Membrane Proteins / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Esterases / physiology*
  • Extracellular Matrix Proteins / physiology*
  • Fibronectins / physiology
  • Gene Expression Regulation, Bacterial
  • Haemophilus Infections / microbiology*
  • Haemophilus influenzae / classification*
  • Haemophilus influenzae / physiology*
  • Laminin / physiology
  • Lipoproteins / physiology*
  • MDS1 and EVI1 Complex Locus Protein
  • Mice
  • Otitis Media / microbiology
  • Protein Binding
  • Proto-Oncogenes / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Vitronectin / physiology


  • Bacterial Outer Membrane Proteins
  • DNA-Binding Proteins
  • Extracellular Matrix Proteins
  • Fibronectins
  • Laminin
  • Lipoproteins
  • MDS1 and EVI1 Complex Locus Protein
  • Mecom protein, mouse
  • Transcription Factors
  • Vitronectin
  • e(P4) lipoprotein, Haemophilus influenzae
  • Esterases