| 11. |
- Spaulding, Caitlin N., et al.
(författare)
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Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions
- 2018
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Ingår i: eLIFE. - : eLife Sciences Publications. - 2050-084X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 12. |
- Sundin, Johanna, 1982-, et al.
(författare)
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Altered faecal and mucosal microbial composition in post-infectious irritable bowel syndrome patients correlates with mucosal lymphocyte phenotypes and psychological distress
- 2015
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Ingår i: Alimentary Pharmacology and Therapeutics. - Hoboken, USA : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 41:4, s. 342-351
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Tidskriftsartikel (refereegranskat)abstract
- Background: A subset of irritable bowel syndrome (IBS) patients, denoted post-infectious IBS (PI-IBS), develop symptoms after an enteric infection. Bacterial dysbiosis and mucosal inflammation have been proposed to be involved in the pathophysiology of this entity.Aim: To characterise the mucosal and faecal microbiota in PI-IBS, general IBS and healthy controls, and to investigate associations between the microbiota and the mucosal immune system.Methods: Mucosal biopsies and faeces were collected from 13 PI-IBS patients, 19 general IBS patients and 16 healthy controls. Global bacterial composition was determined by generating 16S rRNA amplicons that were examined by phylogenetic microarray hybridisation, principal component and redundancy analysis. We correlated previously reported lymphocyte proportions with the microbiota.Results: Faecal microbiota composition of PI-IBS patients differed significantly from both general IBS patients and healthy controls (P < 0.02). Both mucosal (P < 0.01) and faecal (P = 0.05) microbial diversity were reduced in PI-IBS compared to healthy controls. In the intraepithelial lymphocytes the previously published proportion of CD8+ CD45RA+ was negatively correlated with mucosal microbial diversity (P < 0.005). The previously published number of lamina propria lymphocytes was negatively correlated with mucosal microbial diversity (P < 0.05). Faecal microbial diversity was significantly negatively correlated with the Hospital Anxiety and Depression scale (P < 0.05).Conclusions: We present data that distinguishes the intestinal microbiota of PI-IBS patients from that of both general IBS patients and HC. The microbial composition is significantly associated with the HADs score and alterations in lymphocyte subsets proportions.
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| 13. |
- Zheng, Weili, et al.
(författare)
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Cryo-Em Structure of Type 1 Pilus
- 2018
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Ingår i: Biophysical Journal. - : Biophysical Society. - 0006-3495 .- 1542-0086. ; 114:3, s. 370a-370a
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Urinary tract infections (UTIs) are caused by a wide range of pathogens, but the most common causative agent of UTIs is uropathogenic Escherichia coli (UPEC). Virtually all uropathogenic strains of E. coli encode filamentous surface adhesive organelles called type 1 pili, which are a subset of Chaperone-usher pathway (CUP) pili. CUP pili are also ubiquitously expressed on the surface of many other Gram-negative bacterial pathogens. They are important virulence factors facilitating host-pathogen interactions that are crucial for the establishment and persistence of an infection, and involved in regulating other key processes such as biofilm formation. We have solved the 4.2 Å resolution cryo-EM structure of the type 1 pilus, which was present as a background contaminant in a prep of type 4 pili. We have taken advantage of the strength of cryo-EM to separate different molecules and conformations present in solution to show that filament images which might otherwise have been discarded as a contaminant can actually be used to build an atomic model. The model reveals the residues that allow a long chain of FimA subunits, linked by the insertion of a β-strand of one subunit into the β-sheet of an adjacent subunit, to coil into a rigid rod. We show that site-specific mutation of these residues reduces the force needed to unwind the rod. Strikingly, one mutation (A22R) which showed the greatest reduction in unwinding force, eliminated bladder infections in a mouse model. This is presumably due to the fact that the altered mechanics of the A22R pilus rod cannot withstand the shear forces due to urinary flow in the bladder and bacteria harboring this mutation are cleared from the bladder. This provides new insights into the important role of pili mechanics in bacterial pathogenesis.
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| 14. |
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| 15. |
- Zommorodi, S, et al.
(författare)
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Understanding abdominal aortic aneurysm epidemiology: socioeconomic position affects outcome
- 2018
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Ingår i: Journal of epidemiology and community health. - : BMJ. - 1470-2738 .- 0143-005X. ; 72:10, s. 904-910
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Tidskriftsartikel (refereegranskat)abstract
- Low socioeconomic position (SEP) has been demonstrated to negatively influence outcome in several cardiovascular patient groups. The aim of this study was to analyse time trends of incidence of intact abdominal aortic aneurysm (iAAA) and ruptured AAA (rAAA), respectively, and to investigate whether SEP had any influence on the probability to present with rupture and, finally, to determine the impact of SEP on outcome.MethodsNationwide population-based study including all individuals with iAAA or rAAA in Sweden during 2001–2015.ResultsThe number of individuals with an AAA was 41 222; the majority were identified as iAAA 33 254 (80.7%) and 7968 (19.3%) as rAAA. Time trends showed decreasing incidence of rAAA but increase in iAAA during the study period. Individuals with low income or low educational level were more likely to present with a rAAA rather than iAAA: OR 2.16 (95 % CI 1.98 to 2.36, p<0.001) and OR 1.33 (95 % CI 1.21 to 1.46, p<0.001), respectively. Low income was also associated with increased 90-day mortality and 1-year mortality after treatment for rAAA, OR 1.42 (95% CI 1.07 to 1.89, p=0.014) and OR 1.39 (95% CI 1.13 to 1.97, p=0.005).ConclusionThis large nationwide study showed a decreasing incidence of rAAA. Individuals with low SEP were found to have an augmented risk of presenting with rAAA rather than iAAA and, in addition, to fare worse after repair. Consequently, SEP should be regarded as a relevant risk factor that should be included in considerations for improved care flow of patients with AAA.
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