The Colonization Strategies of Nontypeable Haemophilus influenzae - Bacterial Colonization Factors and Vaccine Development
Author
Summary, in English
We have shown that the NTHi virulence factor Protein E mediates innate immune evasion by interacting with the C-terminus of host complement down-regulatory protein vitronectin. This interaction delayed the formation of the membrane attack complex on the bacterial surface and increased the bacterial serum-resistance. Furthermore, we identified a novel surface-exposed virulence factor designated Haemophilus Protein F that also sequesters vitronectin on the surface of the bacteria, thus rendering the pathogen more serum-resistant. Moreover, we have revealed that Protein F mediates bacterial adherence to primary human bronchial cells and to the extracellular matrix protein laminin. Isogenic mutants devoid of Protein F were observed to adhere significantly less to vitronectin, epithelial cells and laminin. These interactions were characterized at the molecular level, and the N-terminus of Protein F was shown to contain the host-interacting region. Finally, we showed that immunization with Protein F conferred increased pulmonary clearance of NTHi in vivo.
In summary, we have identified, and at the molecular level characterized, novel virulence factors that may be suitable for future vaccine development.
Department/s
Publishing year
2015
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2015:13
Full text
- Available as PDF - 26 MB
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Document type
Dissertation
Publisher
Clinical Microbiology, Malmö, Lund University
Topic
- Microbiology in the medical area
Keywords
- ABC-transporter
- bacterial colonization
- Haemophilus influenzae
- Haemophilus Protein F
- laminin
- NTHi
- pathogenesis
- vaccine
- virulence
- vitronectin.
Status
Published
Research group
- Clinical Microbiology, Malmö
Supervisor
- Kristian Riesbeck
- Arne Forsgren
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-7619-093-7
Defence date
30 January 2015
Defence time
13:00
Defence place
Main lecture hall of the Pathology building, Jan Waldenströms gata 59, Malmö
Opponent
- Joachim Reidl (Professor)