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Fimbria-mediated adherence and hemagglutination of Haemophilus influenzae
S M van Ham1, L van Alphen, F R Mooi
1Department of Medical Microbiology, University of Amsterdam, Netherlands.
Abstract:
The gram-negative bacterium Haemophilus influenzae expresses morphologically and functionally distinct types of fimbriae, of which the LKP fimbriae mediate hemagglutination and adherence to human epithelial cells but hamper mucosal invasion. Therefore, the both in vivo and in vitro observed fimbrial phase variation may contribute to the pathogenesis of the infection. The existence of greater than 14 LKP serotypes hampers vaccine development based on fimbriae, since a monovalent fimbria vaccine confers protection against only the homologous strain. Cloning of the fimbrial genes in Escherichia coli results in the expression of morphologically intact fimbriae. Analysis of the cloned DNA indicates that a fimbrial gene cluster is necessary for formation of complete fimbriae and for fimbria-mediated adherence. The gene encoding the subunit is highly conserved among H. influenzae and belongs to the family of E. coli fimbriae. The phase variation is transcriptionally regulated by variation of the length of the reiterated sequence that forms the promoter region of the subunit gene.
Insights
Haemophilus influenzae uses LKP fimbriae for adherence but not invasion. Fimbrial phase variation, regulated by promoter sequence length, impacts pathogenesis and complicates vaccine development due to numerous serotypes.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Vaccinology
Background:
- Haemophilus influenzae possesses distinct fimbriae, including LKP fimbriae, which mediate hemagglutination and adherence to human epithelial cells.
- LKP fimbriae appear to impede mucosal invasion by H. influenzae.
- Fimbrial phase variation in H. influenzae is observed both in vivo and in vitro, suggesting a role in infection pathogenesis.
Purpose of the Study:
- To investigate the role of fimbrial phase variation in Haemophilus influenzae pathogenesis.
- To analyze the genetic basis of LKP fimbriae formation and adherence.
- To understand the mechanism regulating fimbrial phase variation.
Main Methods:
- Cloning of fimbrial genes into Escherichia coli for expression analysis.
- DNA analysis to identify gene clusters essential for fimbriae formation and adherence.
- Investigation of the promoter region of the fimbrial subunit gene to understand phase variation regulation.
Main Results:
- Cloning of fimbrial genes in E. coli resulted in morphologically intact fimbriae.
- A specific fimbrial gene cluster is required for complete fimbriae formation and adherence.
- The fimbrial subunit gene is conserved among H. influenzae strains and similar to E. coli fimbriae.
- Fimbrial phase variation is transcriptionally controlled by alterations in the length of a reiterated sequence within the promoter region.
Conclusions:
- Fimbrial phase variation in H. influenzae, regulated transcriptionally by promoter length, contributes to pathogenesis.
- The LKP fimbriae's role in adherence and potential hindrance of invasion highlights their importance in infection.
- The high diversity of LKP serotypes presents a significant challenge for developing effective fimbria-based vaccines.