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Impairment of the biomechanical compliance of P pili: a novel means of inhibiting uropathogenic bacterial infections?
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
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2012 (engelsk)Inngår i: European Biophysics Journal, ISSN 0175-7571, E-ISSN 1432-1017, Vol. 41, nr 3, s. 285-295Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Berlin: Springer, 2012. Vol. 41, nr 3, s. 285-295
Emneord [en]
Bacterial adhesion, Force-measuring optical tweezers, Antimicrobial, Single organelle, Pili recoiling
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Identifikatorer
URN: urn:nbn:se:umu:diva-51266DOI: 10.1007/s00249-011-0784-2ISI: 000300496600003PubMedID: 22237603OAI: oai:DiVA.org:umu-51266DiVA, id: diva2:478246
Tilgjengelig fra: 2012-01-16 Laget: 2012-01-16 Sist oppdatert: 2018-06-08bibliografisk kontrollert

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