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Impairment of the biomechanical compliance of P pili: a novel means of inhibiting uropathogenic bacterial infections?
Umeå University, Faculty of Science and Technology, Department of Physics. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
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2012 (English)In: European Biophysics Journal, ISSN 0175-7571, E-ISSN 1432-1017, Vol. 41, no 3, 285-295 p.Article in journal (Refereed) Published
Abstract [en]

Gram-negative bacteria often initiate their colonization by use of extended attachment organelles, so called pili. When exposed to force, the rod of helix-like pili has been found to be highly extendable, mainly attributed to uncoiling and recoiling of its quaternary structure. This provides the bacteria with the ability to redistribute an external force among a multitude of pili, which enables them to withstand strong rinsing flows, which, in turn, facilitates adherence and colonization processes critical to virulence. Thus, pili fibers are possible targets for novel antibacterial agents. By use of a substance that compromises compliance of the pili, the ability of bacteria to redistribute external forces can be impaired, so they will no longer be able to resist strong urine flow and thus be removed from the host. It is possible such a substance can serve as an alternative to existing antibiotics in the future or be a part of a multi-drug. In this work we investigated whether it is possible to achieve this by targeting the recoiling process. The test substance was purified PapD. The effect of PapD on the compliance of P pili was assessed at the single organelle level by use of force-measuring optical tweezers. We showed that the recoiling process, and thus the biomechanical compliance, in particular the recoiling process, can be impaired by the presence of PapD. This leads to a new concept in the search for novel drug candidates combating uropathogenic bacterial infections-"coilicides", targeting the subunits of which the pilus rod is composed.

Place, publisher, year, edition, pages
Berlin: Springer, 2012. Vol. 41, no 3, 285-295 p.
Keyword [en]
Bacterial adhesion, Force-measuring optical tweezers, Antimicrobial, Single organelle, Pili recoiling
National Category
Physical Sciences Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-51266DOI: 10.1007/s00249-011-0784-2ISI: 000300496600003PubMedID: 22237603OAI: oai:DiVA.org:umu-51266DiVA: diva2:478246
Available from: 2012-01-16 Created: 2012-01-16 Last updated: 2017-12-08Bibliographically approved

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Klinth, Jeanna EAlmqvist, FredrikUhlin, Bernt EricAxner, Ove

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Department of PhysicsUmeå Centre for Microbial Research (UCMR)Department of Molecular Biology (Faculty of Science and Technology)Molecular Infection Medicine Sweden (MIMS)Centre for Biomedical Engineering and Physics (CMTF)Department of ChemistryDepartment of Molecular Biology (Faculty of Medicine)
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