Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions
| Autor: | Olivera Francetic, Scott J. Hultgren, Henry L. Schreiber, Caitlin N. Spaulding, Karen W. Dodson, Weili Zheng, Pontus Svenmarker, Fengbin Wang, Edward H. Egelman, Jennie E Hazen, Magnus Andersson, Matt S. Conover, Areli Luna-Rico |
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| Přispěvatelé: | Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), University of Virginia [Charlottesville], Umeå University, Biochimie des Interactions Macromoléculaires / Biochemistry of Macromolecular Interactions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from the National Institutes of Health [GM122510 (EHE), AI048689 and DK064540 (SJH), 1F31DK107057 (CNS), and DK101171-02 (MSC)], the Swedish Research Council 621-2013-5379 (MA) and the Agence Nationale de la Reserche ANR-14-CE09-0004 (OF). ALR was funded by the Pasteur Paris University PhD program. The cryo-EM work was conducted at the Molecular Electron Microscopy Core facility at the University of Virginia, which is supported by the School of Medicine and built with NIH grant G20-RR31199. The Titan Krios and Falcon II direct electron detector within the Core were purchased with NIH SIG S10-RR025067 and S10-OD018149, respectively., ANR-14-CE09-0004,FiberSpace,Pili de type IV et pseudopili: structure, dynamique, assemblage et fonction moléculaire(2014), University of Virginia, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Structural Biology and Molecular Biophysics UTI MESH: Uropathogenic Escherichia coli/ultrastructure Bacterial Adhesion Pilus Mice Structural Biology biophysics Uropathogenic Escherichia coli structural biology MESH: Animals Biology (General) Pathogen Escherichia coli Infections Strukturbiologi Microbiology and Infectious Disease biology MESH: Urinary Tract Infections/microbiology General Neuroscience MESH: Fimbriae Proteins/metabolism Annan fysik General Medicine MESH: Adhesins Bacterial / ultrastructure 3. Good health [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology type 1 pili MESH: Escherichia coli Infections/microbiology Host-Pathogen Interactions Urinary Tract Infections Medicine Fimbriae Proteins MESH: Adhesins Bacterial / metabolism MESH: Cryoelectron Microscopy Research Article Functional role MESH: Fimbriae Bacterial/metabolism Other Physics Topics QH301-705.5 Science infectious disease 030106 microbiology CUP pili General Biochemistry Genetics and Molecular Biology Microbiology Microbiology in the medical area MESH: Fimbriae Proteins/genetics 03 medical and health sciences Mikrobiologi inom det medicinska området Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Fimbriae Bacterial/ultrastructure MESH: Bacterial Adhesion Adhesins Bacterial MESH: Mice mouse General Immunology and Microbiology Chaperone-usher pathway pili Cryoelectron Microscopy microbiology MESH: Host-Pathogen Interactions E. coli biochemical phenomena metabolism and nutrition MESH: Uropathogenic Escherichia coli/physiology Disease Models Animal 030104 developmental biology Fimbriae Bacterial Chaperone (protein) biology.protein bacteria cryo-EM UPEC MESH: Disease Models Animal |
| Zdroj: | eLife eLife, eLife Sciences Publication, 2018, 7, pp.e31662. ⟨10.7554/eLife.31662⟩ eLife, Vol 7 (2018) eLife, 2018, 7, pp.e31662. ⟨10.7554/eLife.31662⟩ |
| ISSN: | 2050-084X |
| Popis: | Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the gut. The pilus rod, comprised of repeating FimA subunits, provides a structural scaffold for displaying the tip adhesin, FimH. We solved the 4.2 Å resolution structure of the type 1 pilus rod using cryo-electron microscopy. Residues forming the interactive surfaces that determine the mechanical properties of the rod were maintained by selection based on a global alignment of fimA sequences. We identified mutations that did not alter pilus production in vitro but reduced the force required to unwind the rod. UPEC expressing these mutant pili were significantly attenuated in bladder infection and intestinal colonization in mice. This study elucidates an unappreciated functional role for the molecular spring-like property of type 1 pilus rods in host-pathogen interactions and carries important implications for other pilus-mediated diseases. eLife digest Escherichia coli, or E. coli for short, is a type of bacteria commonly found in the guts of people and animals. Certain types of E. coli can cause urinary tract infections (UTIs): they travel from the digestive tract up to the bladder (and sometimes to the kidneys) where they provoke painful symptoms. To cause the infection, the bacteria must become solidly attached to the lining of the bladder; otherwise they will get flushed out whenever urine is expelled. Pili are hair-like structures that cover a bacterium and allow it to attach to surfaces. E. coli has many different types of pili, but one seems particularly important in UTIs: type 1 pili. These pili are formed of subunits that assemble into a long coil-shaped rod, which is tipped by adhesive molecules that can stick to body surfaces. The current hypothesis is that the pili act as shock absorbers: when the bladder empties, the pili’s coil-like structure can unwind into a flexible straight fiber. This would take some of the forces off the adhesive molecules that are attached to the bladder, and help the bacteria to remain in place when urine flows out. However, the exact structure of type 1 pili is still unclear, and the essential role of their coil-like shape unconfirmed. Here, Spaulding, Schreiber, Zheng et al. use a microscopy method called cryo-EM to reveal the structure of the type 1 pili at near atomic-level, and identify the key units necessary for their coiling properties. The experiments show that pili with certain mutations in these units unwind much more easily when the bacteria carrying them are ‘tugged on’ with molecular tweezers. The bacteria with mutant pili are also less able to cause UTIs in mice. The coiling ability of the type 1 pili is therefore essential for E. coli to invade and colonize the bladder. Every year, over 150 million people worldwide experience a UTI; for 25% of women, the infection regularly returns. Antibiotics usually treat the problem but bacteria are becoming resistant to these drugs. New treatments could be designed if scientists understand what roles pili play in the infection mechanisms. |
| Databáze: | OpenAIRE |
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