Outer membrane protein P1 is the CEACAM-binding adhesin of Haemophilus influenzae

Arnaud Kengmo Tchoupa1, Sabine Lichtenegger2, Joachim Reidl2

  • 1Lehrstuhl für Zellbiologie, Universität Konstanz, Konstanz, Germany.

Insights

Haemophilus influenzae uses outer membrane protein P1 to bind human CEACAMs, facilitating bacterial entry into epithelial cells. This study identifies OMP P1 as the key invasin, crucial for H. influenzae pathogenesis.

Area of Science:

  • Microbiology
  • Cell Biology
  • Pathogenesis

Background:

  • Haemophilus influenzae is a Gram-negative pathogen that colonizes the upper respiratory tract.
  • Bacterial uptake into epithelial cells is mediated by binding to carcinoembryonic antigen-related cell adhesion molecules (CEACAMs).
  • Outer membrane protein P5 was previously suspected to mediate CEACAM binding.

Purpose of the Study:

  • To identify the specific outer membrane protein responsible for Haemophilus influenzae binding to CEACAMs.
  • To elucidate the role of this protein in bacterial invasion of epithelial cells.
  • To determine the specificity of the CEACAM-binding interaction.

Main Methods:

  • Screening of Haemophilus influenzae outer membrane protein mutants for CEACAM binding.
  • Heterologous expression of outer membrane proteins in Escherichia coli.
  • Assessing bacterial attachment and internalization into CEACAM-expressing epithelial cells.

Main Results:

  • Lack of outer membrane protein P1 abrogated CEACAM binding and epithelial cell engulfment.
  • Ectopic expression of OMP P1 in E. coli induced CEACAM binding and cell internalization.
  • OMP P1 selectively binds human CEACAMs, not homologs from other mammals.

Conclusions:

  • Outer membrane protein P1 is the bona fide CEACAM-binding invasin of Haemophilus influenzae.
  • OMP P1 plays a critical role in H. influenzae pathogenesis by mediating CEACAM-dependent invasion.
  • This finding represents the first evidence for the involvement of OMP P1 in H. influenzae pathogenesis.

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