title: Impairment of the biomechanical compliance of P pili: a novel means of inhibiting uropathogenic bacterial infections?
abstract: 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.
authors.affiliation: Department of Physics, Umeå University, 901 87 Umeå, Sweden. jeanna.klinth@physics.umu.se
authors.forename: Jeanna E
authors.initials: JE
authors.lastname: Klinth
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Pinkner
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hultgren
authors.forename: Fredrik
authors.initials: F
authors.lastname: Almqvist
authors.forename: Bernt Eric
authors.initials: BE
authors.lastname: Uhlin
authors.forename: Ove
authors.initials: O
authors.lastname: Axner
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001696:Biomechanical Phenomena; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000187:drug effects* / Q000378:metabolism; D055595:Mechanical Phenomena; D008958:Models, Molecular; D052898:Optical Tweezers; D011487:Protein Conformation; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins