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Structure and function of enterotoxigenic Escherichia coli fimbriae from differing assembly pathways
Umeå University, Faculty of Science and Technology, Department of Physics. (The Biophysics and Biophotonics group)
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
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2015 (English)In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 95, no 1, 116-126 p.Article in journal (Refereed) Published
Abstract [en]

Pathogenic enterotoxigenic Escherichia coli (ETEC) are the major bacterial cause of diarrhea in young children in developing countries and in travelers, causing significant mortality in children. Adhesive fimbriae are a prime virulence factor for ETEC, initiating colonization of the small intestinal epithelium. Similar to other Gram-negative bacteria, ETEC express one or more diverse fimbriae, some assembled by the chaperone-usher pathway and others by the alternate chaperone pathway. Here, we elucidate structural and biophysical aspects and adaptations of each fimbrial type to its respective host niche. CS20 fimbriae are compared with colonization factor antigen I (CFA/I) fimbriae, which are two ETEC fimbriae assembled via different pathways, and with P-fimbriae from uropathogenic E.coli. Many fimbriae unwind from their native helical filament to an extended linear conformation under force, thereby sustaining adhesion by reducing load at the point of contact between the bacterium and the target cell. CFA/I fimbriae require the least force to unwind, followed by CS20 fimbriae and then P-fimbriae, which require the highest unwinding force. We conclude from our electron microscopy reconstructions, modeling and force spectroscopy data that the target niche plays a central role in the biophysical properties of fimbriae that are critical for bacterial pathophysiology.

Place, publisher, year, edition, pages
John Wiley & Sons, 2015. Vol. 95, no 1, 116-126 p.
Keyword [en]
fimbriae, pili, macromolecules, optical tweezers
National Category
Other Physics Topics Medical and Health Sciences
URN: urn:nbn:se:umu:diva-95561DOI: 10.1111/mmi.12847ISI: 000346656200008PubMedID: 25355550OAI: diva2:759753
Swedish Research Council, 621-2013-5379
Available from: 2014-10-31 Created: 2014-10-31 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

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Mortezaei, NargesShirdel, MariamBhupender, SinghUhlin, Bernt EricAndersson, Magnus
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