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The variable P5 proteins of typeable and non-typeable Haemophilus influenzae target human CEACAM1
D J Hill1, M A Toleman, D J Evans
1Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
Abstract:
Haemophilus influenzae, a commensal of the human respiratory mucosa, is an important cause of localized and systemic infections. We have recently shown that numerous strains of capsulate (typeable) and acapsulate (non-typeable) H. influenzae target the carcinoembryonic antigen (CEA) family of cell adhesion molecules (CEACAMs). Moreover, the ligands appeared to be antigenically variable and, when using viable typeable bacteria, their adhesive functions were inhibited by the presence of capsule. In this report, we show that the antigenically variable outer membrane protein, P5, expressed by typeable and non-typeable H. influenzae targets human CEACAM1. Variants and mutants lacking the expression of P5 of all strains tested were unable to target purified soluble receptors. A non-typeable strain that did not interact with CEACAM1 was made adherent to both the soluble receptors and CEACAM1-transfected Chinese hamster ovary cells by transformation with the P5 gene derived from the adherent typeable strain Rd. However, several H. influenzae mutants lacking P5 expression continued to bind the cell-bound CEACAM1 receptors. These observations suggest that (i) CEACAM1 alone can support P5 interactions and (ii) some strains contain additional ligands with the property to target CEACAM1 but require the receptor in the cellular context. The identification of a common ligand in diverse strains of H. influenzae and the presence of multiple ligands for the same receptor suggests that targeting of members of the CEACAM family of receptors may be of primary significance in colonization and pathogenesis of H. influenzae strains.
Insights
Haemophilus influenzae uses the outer membrane protein P5 to target human CEACAM1, a key adhesion molecule. This interaction is crucial for bacterial colonization and infection, with some strains having additional CEACAM1 ligands.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Haemophilus influenzae causes various infections and targets carcinoembryonic antigen (CEA) family molecules (CEACAMs).
- Bacterial ligands for CEACAMs are antigenically variable and can be inhibited by capsule presence.
Purpose of the Study:
- To identify the specific ligand on H. influenzae that targets CEACAM1.
- To investigate the role of the outer membrane protein P5 in H. influenzae adhesion to CEACAM1.
Main Methods:
- Testing P5 expression in typeable and non-typeable H. influenzae strains.
- Assessing bacterial adherence to purified soluble CEACAM1 and CEACAM1-transfected cells.
- Utilizing gene transformation to introduce P5 into non-adherent strains.
Main Results:
- The outer membrane protein P5 from H. influenzae directly targets human CEACAM1.
- Mutants lacking P5 showed reduced or abolished binding to soluble CEACAM1.
- Some H. influenzae strains possess additional CEACAM1 ligands that require cellular context.
Conclusions:
- CEACAM1 is a direct target for H. influenzae via the P5 protein.
- Multiple ligands targeting CEACAM1 may exist in H. influenzae, contributing to colonization and pathogenesis.
- Understanding these interactions is vital for developing strategies against H. influenzae infections.