Change search
ReferencesLink to record
Permanent link

Direct link
P-fimbriae in the presence of anti-PapA antibodies: new insight of antibodies action against pathogens
Umeå University, Faculty of Science and Technology, Department of Physics. (The Biophysics and Biophotonics group)
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
Boston University School of Medicine.
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
Show others and affiliations
2013 (English)In: Scientific Reports, ISSN 2045-2322, Vol. 3, Article Number: 3393- p.Article in journal (Refereed) Published
Abstract [en]

Uropathogenic strains of Escherichia coli establish urinary tract infections by attaching to host epithelial cells using adhesive organelles called fimbriae. Fimbriae are helix-like structures with a remarkable adaptability, offering safeguarding for bacteria exposed to changing fluid forces in the urinary tract. We challenged this property of P-fimbriae by cross-linking their subunits with shaft-specific antibodies and measuring the corresponding force response at a single organelle level. Our data show compromised extension and rewinding of P-fimbriae in the presence of antibodies and reduced fimbrial elasticity, which are important properties of fimbriae contributing to the ability of bacteria to cause urinary tract infections. The reduced elasticity found by cross-linking fimbrial subunits could thus be another assignment for antibodies; in addition to marking bacteria as foreign, antibodies physically compromise fimbrial function. We suggest that our assay and results will be a starting point for further investigations aimed at inhibiting sustained bacterial adhesion by antibodies.

Place, publisher, year, edition, pages
Nature Publishing Group, 2013. Vol. 3, Article Number: 3393- p.
Keyword [en]
optical tweezers, E coli, antibodies, IgG, adhesion
National Category
Other Physics Topics Immunology Microbiology Biophysics
Research subject
URN: urn:nbn:se:umu:diva-82964DOI: 10.1038/srep03393OAI: diva2:664198
Swedish Research Council, VR-MH 2010-3031, VR-NT 2012-4638, 349-2007-8673
Available from: 2013-11-14 Created: 2013-11-14 Last updated: 2016-04-29Bibliographically approved
In thesis
1. Exploring the impact of antibodies on the mechanics of bacterial fimbriae
Open this publication in new window or tab >>Exploring the impact of antibodies on the mechanics of bacterial fimbriae
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The discovery of antibiotics in 1928 seemed like a win in the battle against infectious diseases. But, the ability of bacterial pathogens to adapt to these life-saving medicines was underestimated. The bacterial evolution, indeed, led to the emergence of antibiotic resistance as soon as the clinical consumption of antibiotics started. Today, certain bacteria including some strains of the gram-negative Escherichia coli are resistant to all major antibiotics. To overcome this problem, identifying new therapeutic targets in bacteria is essential, which necessitates scrutinizing the bacterial infection mechanism. An initial step in the bacterial infection mechanism is identification of and adherence to host tissue. Thus, blocking bacterial adhesion is considered as a potential target in the battle against infectious diseases. Gram-negative bacteria generally establish their adhesion by variety of proteinaceous structures known as fimbriae. The strains of Escherichia coli associated with gastrointestinal and urinary tract infections, for instance, colonize their host via a variety of adhesion fimbriae. These adhesion organelles are comprised of subunits assembled into a helix-like structure with remarkable biomechanical properties. For example, fimbriae can be significantly extended under force and are therefore very flexible. Fimbrial flexibility is considered to be beneficial for attachment and adhesion of bacteria in fluidic regions.

The aims of this thesis are: to provide insight into the structural and biomechanical differences of fimbriae expressed by enterotoxigenic and uropathogenic Escherichia coli, and to investigate how fimbrial mechanics are affected in the presence of anti-fimbrial antibodies. To achieve these aims we put together data acquired using different technical approaches. We used force measuring optical tweezers to characterize the force-extension responses of fimbriae in the absence and presence of antibodies. High-resolution imaging was employed to explore the structural features of fimbriae as well as monitoring the antibody-fimbriae interactions. Our results demonstrate that each type of fimbria explored shows unique force spectroscopy responses. For example, the fimbriae expressed by uropathogenic Escherichia coli require a higher unwinding force in comparison to enterotoxigenic Escherichia coli fimbriae. These observations suggest that bacteria adapt to the environment wherein they establish colonization by expressing fimbriae with different biophysical features. Such evolutionary adaptation can thereby help in the bacterial adhesion process. Furthermore, we found that antibodies significantly alter the biophysical features of fimbriae, implying that antibodies significantly interfere with the mechanics of fimbriae. We suggest further elucidation of how antibodies disrupt fimbrial mechanics, providing insights for the development of antibody-based therapeutics.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2016. 70 p.
National Category
urn:nbn:se:umu:diva-119694 (URN)978-91-7601-464-6 (ISBN)
Public defence
2016-05-20, Naturvetarhuset N420, Umeå, 13:00 (English)
Available from: 2016-04-29 Created: 2016-04-25 Last updated: 2016-04-29Bibliographically approved

Open Access in DiVA

fulltext(1875 kB)247 downloads
File information
File name FULLTEXT01.pdfFile size 1875 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Mortezaei, NargesSingh, BhupenderUhlin, Bernt EricAndersson, Magnus
By organisation
Department of PhysicsDepartment of Molecular Biology (Faculty of Medicine)Molecular Infection Medicine Sweden (MIMS)
In the same journal
Scientific Reports
Other Physics TopicsImmunologyMicrobiologyBiophysics

Search outside of DiVA

GoogleGoogle Scholar
Total: 247 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 277 hits
ReferencesLink to record
Permanent link

Direct link