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Journal articleAllegretti JR, Hurtado J, Carrellas M, et al., 2020,
121 ULCERATIVE COLITIS PATIENTS ACHEIVE MORE ROBUST ENGRAFTMENT COMPARED TO PATIENTS WITH CROHN'S DISEASE AFTER FECAL MICROBIOTA TRANSPLANTATION FOR THE TREATMENT OF RECURRENT C. DIFFICLE INFECTION
, Gastroenterology, Vol: 158, Pages: S-22, ISSN: 0016-5085 -
Journal articleFurniss RCD, Kostrzewa M, Mavridou DAI, et al., 2020,
The clue is in the lipid A: Rapid detection of colistin resistance
, PLoS Pathogens, Vol: 16, ISSN: 1553-7366 -
Journal articleVakili M, Aliyali M, Mortezaee V, et al., 2020,
Relationship between spirometry results and colonisation of Aspergillus species in allergic asthma
, CLINICAL RESPIRATORY JOURNAL, Vol: 14, Pages: 748-757, ISSN: 1752-6981 -
Journal articleRitchie AI, Singanayagam A, 2020,
Immunosuppression for hyperinflammation in COVID-19: a double-edged sword?
, LANCET, Vol: 395, Pages: 1111-1111, ISSN: 0140-6736- Author Web Link
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- Citations: 190
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Journal articleJégouzo SAF, Nelson C, Hardwick T, et al., 2020,
Mammalian lectin arrays for screening host–microbe interactions
, Journal of Biological Chemistry, Vol: 295, Pages: 4541-4555, ISSN: 0021-9258Many members of the C-type lectin family of glycan-binding receptors have been ascribed roles in the recognition of microorganisms and serve as key receptors in the innate immune response to pathogens. Other mammalian receptors have become targets through which pathogens enter target cells. These receptor roles have often been documented with binding studies involving individual pairs of receptors and microorganisms. To provide a systematic overview of interactions between microbes and the large complement of C-type lectins, here we developed a lectin array and suitable protocols for labeling of microbes that could be used to probe this array. The array contains C-type lectins from cow, chosen as a model organism of agricultural interest for which the relevant pathogen–receptor interactions have not been previously investigated in detail. Screening with yeast cells and various strains of both Gram-positive and -negative bacteria revealed distinct binding patterns, which in some cases could be explained by binding to lipopolysaccharides or capsular polysaccharides, but in other cases they suggested the presence of novel glycan targets on many of the microorganisms. These results are consistent with interactions previously ascribed to the receptors, but they also highlight binding to additional sugar targets that have not previously been recognized. Our findings indicate that mammalian lectin arrays represent unique discovery tools for identifying both novel ligands and new receptor functions.
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Conference paperXu X, van Sorge N, van der Lans S, et al., 2020,
Structural and Interaction Insight in <it>Streptococcal</it> beta C Proteins
, Annual Meeting on Experimental Biology, Publisher: WILEY, ISSN: 0892-6638 -
Journal articleSchuster CF, Wiedemann DM, Kirsebom FCM, et al., 2020,
High‐throughput transposon sequencing highlights the cell wall as an important barrier for osmotic stress in methicillin resistant Staphylococcus aureus and underlines a tailored response to different osmotic stressors
, Molecular Microbiology, Vol: 113, Pages: 699-717, ISSN: 0950-382XStaphylococcus aureus is an opportunistic pathogen that can cause soft tissue infections but is also a frequent cause of foodborne illnesses. One contributing factor for this food association is its high salt tolerance allowing this organism to survive commonly used food preservation methods. How this resistance is mediated is poorly understood, particularly during long‐term exposure. In this study, we used TN‐seq to understand how the responses to osmotic stressors differ. Our results revealed distinctly different long‐term responses to NaCl, KCl and sucrose stresses. In addition, we identified the DUF2538 domain containing gene SAUSA300_0957 (gene 957) as essential under salt stress. Interestingly, a 957 mutant was less susceptible to oxacillin and showed increased peptidoglycan crosslinking. The salt sensitivity phenotype could be suppressed by amino acid substitutions in the transglycosylase domain of the penicillin binding protein Pbp2, and these changes restored the peptidoglycan crosslinking to WT levels. These results indicate that increased crosslinking of the peptidoglycan polymer can be detrimental and highlight a critical role of the bacterial cell wall for osmotic stress resistance. This study will serve as a starting point for future research on osmotic stress response and help develop better strategies to tackle foodborne staphylococcal infections.
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Journal articleChorev DS, Tang H, Rouse SL, et al., 2020,
The use of sonicated lipid vesicles for mass spectrometry of membrane protein complexes
, NATURE PROTOCOLS, Vol: 15, Pages: 1690-1706, ISSN: 1754-2189- Author Web Link
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- Citations: 17
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Journal articleAllegretti JR, Kassam Z, Mullish BH, et al., 2020,
Effects of fecal microbiota transplantation with oral capsules in obese patients
, Clinical Gastroenterology and Hepatology, Vol: 18, Pages: 855-863.e2, ISSN: 1542-3565Background & AimsStudies in mice have shown that the intestinal microbiota can contribute to obesity via the anorexigenic gut hormone glucagon-like peptide 1 (GLP1) and bile acids, which affect lipid metabolism. We performed a randomized, placebo-controlled pilot study of the effects of fecal microbiota transplantation (FMT) in obese, metabolically uncompromised patients.MethodsWe performed a double-blind study of 22 obese patients (body mass index [BMI] ≥ 35kg/m2) without a diagnosis of diabetes, non-alcoholic steatohepatitis, or metabolic syndrome. Participants were randomly assigned (1:1) to groups that received FMT by capsules (induction dose of 30 capsules at week 4 and maintenance dose of 12 capsules at week 8) or placebo capsules. FMT capsules were derived from a single, lean donor (BMI, 17.5 kg/m2). Patients were followed through week 26; the primary outcome was safety. Stool and serum samples were collected from patients at baseline and at weeks 1, 4, 6, 8 and 12 after administration of the first dose of FMT or placebo and analyzed by 16S RNA gene sequencing. Stool and serum samples were analyzed for metabolomics by liquid chromatography-mass spectrometry. Additional outcomes were change in area under the curve for GLP1 at week 12.ResultsWe observed no significant differences in adverse events between patients who received FMT vs placebo. There was no increase in the area under the curve of GLP1 in either group. Patients who received FMT had sustained shifts in microbiomes associated with obesity toward those of the donor (P<.001). Patients who received FMT had a sustained decrease in stool levels of taurocholic acid (P<.05), compared with baseline; bile acid profiles began to more closely resemble those of the donor. We did not observe significant changes in mean BMI at week 12 in either group.ConclusionsIn a placebo-controlled pilot study, we found that FMT capsules (derived from a lean donor) were safe but did not reduce BMI in obese metabol
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Journal articleSanchez Garrido J, Slater SL, Clements A, et al., 2020,
Vying for the control of inflammasomes: the cytosolic frontier of enteric bacterial pathogen - host interactions
, Cellular Microbiology, Vol: 22, Pages: 1-19, ISSN: 1462-5814Enteric pathogen-host interactions occur at multiple interfaces,includingthe intestinal epitheliumand deeper organsof the immune system. Microbial ligands and activities are detected by host sensorsthat elicit a range of immune responses. Membrane-bound Toll-Like Receptors (TLRs) and cytosolic inflammasomepathways are key signal transducers that trigger production of pro-inflammatory molecules such as cytokines and chemokinesand regulate cell deathin response to infection. In recent years, the inflammasomes have emerged as a key frontier in the tusslebetween bacterial pathogens and the host. Inflammasomes are complexes that activate caspase-1and are regulated by related caspases, such as caspase-11, -4, -5 and -8.Importantly, enteric bacterial pathogens can actively engage or evade inflammasome signalling systems. Extracellular, vacuolar and cytosolic bacteria have developed divergent strategies to subvert inflammasomes. While some pathogens take advantage of inflammasomeactivation(e.g. Listeria monocytogenes, Helicobacter pylori), others(e.g. E. coli, Salmonella, Shigella, Yersinia sp.) deploy a range of virulence factors, mainly type 3 secretion system (T3SS) effectors, that subvert or inhibit inflammasomes. In this review we focus on inflammasomepathwaysand their immune functions and discuss how enteric bacterial pathogens interact with them.These studies have not only shed light on the inflammasome-mediated immunity, but also the exciting area of mammalian cytosolic immune
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