Article
Biochemistry & Molecular Biology
Florian Stieglitz, Ralf Gerhard, Rabea Hoenig, Klaudia Giehl, Andreas Pich
Summary: A Clostridioides difficile infection (CDI) is a common hospital-acquired infection worldwide. The virulence factors TcdA and TcdB inhibit small Rho-GTPases, leading to cytopathic effects, colon epithelium barrier dysfunction, and inflammation. A large-scale phosphoproteomic study revealed the central role of RAS in the glucosyltransferase-independent effect of TcdB, and identified apolipoprotein C-III (APOC3) as a potential crucial factor in CDI-induced inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Sebastian Heber, Lara Barthold, Jan Baier, Panagiotis Papatheodorou, Giorgio Fois, Manfred Frick, Holger Barth, Stephan Fischer
Summary: C. difficile produces toxins TcdA and TcdB, which cause CDAD by targeting small GTPases and disrupting intestinal epithelial barrier. Conventional antibiotics do not target these toxins, therefore directly targeting the exotoxins provides a promising treatment approach. Recent findings show that ambroxol reduces toxin-induced cytotoxicity and glucosylation, and could be considered as a therapeutic option for CDAD.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Mojtaba Moosavian, Razieyeh Keshavarzi, Effat Abbasi Montazeri, Eskandar Hajiani
Summary: This study investigated the prevalence of Clostridioides difficile in patients with suspected C. difficile infections using culture, M-PCR, and LAMP methods. The results showed that the LAMP assay is a good method for direct detection of toxigenic C. difficile strains from stool specimens.
Article
Immunology
Baohua Chen, Kay Perry, Rongsheng Jin
Summary: This study reports the identification of two critical epitopes on the virulence factor TcdA and sheds new insights into the neutralizing mechanisms of two potent camelid antibodies against TcdA. These findings provide potential targets for the development of epitope-focused vaccines against TcdA.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Hamideh Raeisi, Masoumeh Azimirad, Hamid Asadzadeh Aghdaei, Amir-Hassan Zarnani, Jalal Abdolalizadeh, Abbas Yadegar, Mohammad Reza Zali
Summary: In this study, phage display was used to select single-chain variable fragments (scFvs) that specifically target the major virulence factors, TcdA and TcdB, of Clostridioides difficile. The selected scFvs showed high neutralizing activity and could decrease the mRNA expression of inflammatory markers in treated cells. Molecular docking revealed that the interaction between scFvs and toxins was mainly restricted to the CROP domain. These findings provide insights for the development of neutralizing scFvs against C. difficile toxins using phage display.
MICROBIOLOGY SPECTRUM
(2023)
Article
Infectious Diseases
Guido Granata, Davide Mariotti, Paolo Ascenzi, Nicola Petrosillo, Alessandra di Masi
Summary: The study demonstrates that toxemia is more common than expected in patients with Clostridioides difficile infection, and specifically that high serum levels of TcdA are correlated with disease severity.
Article
Biochemistry & Molecular Biology
Lara Barthold, Sebastian Heber, Christoph Q. Schmidt, Marion Gradl, Gilbert Weidinger, Holger Barth, Stephan Fischer
Summary: Rising incidences and mortalities of Clostridioides difficile infections (CDIs) have raised concerns. In this study, the protective effect of human antimicrobial peptide alpha-defensin-6 against CDI toxins TcdA and TcdB was demonstrated. The peptide prevented toxin-mediated glucosylation of Rho-GTPases, protecting cells, epithelial barriers, and zebrafish embryos from toxic effects. It was found that alpha-defensin-6 rapidly sequesters the toxin into complexes, preventing its cytotoxic activity. These findings contribute to the understanding of how human peptides neutralize bacterial protein toxins and may guide the development of novel therapeutic options against CDIs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Isabel Marquardt, Josefine Jakob, Jessica Scheibel, Julia Danielle Hofmann, Frank Klawonn, Meina Neumann-Schaal, Ralf Gerhard, Dunja Bruder, Lothar Jaensch
Summary: C. difficile toxins can efficiently activate human mucosal-associated invariant T (MAIT) cells, especially CDTb provokes significant activation. This response partially depends on MR1 and monocytes, and may contribute to the pathophysiology of CDAC by inducing cytotoxicity.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Medicine, Research & Experimental
Khalid M. Aljarallah, Sezanur Rahman
Summary: This study identified potential antagonists for the two major toxins of Clostridium difficile, TcdA and TcdB, from a library of plant-derived compounds through computational screening. The top 10 compounds for each target were found to have higher binding affinities compared to their positive controls, suggesting them to be good drug candidates against C. difficile toxins. Further validation with in vivo and in vitro experiments is needed before considering these potential inhibitors as prospective therapeutics.
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE
(2021)
Article
Food Science & Technology
Aria Aminzadeh, Rene Jorgensen
Summary: By optimizing culture parameters and purification methods, the production yield of native toxin A and toxin B from Clostridioides difficile was significantly improved, resulting in high concentrations of toxin B. Additionally, optimal conditions for improving protein stability during storage were identified.
Article
Chemistry, Analytical
Waleed A. Hassanain, Julia Spoors, Christopher L. Johnson, Karen Faulds, Neil Keegan, Duncan Graham
Summary: The study introduces a novel testing platform for the rapid and simultaneous detection of two specific biomarkers of Clostridium difficile infection, providing a rapid, selective, sensitive, and cost-effective clinical evaluation method for CDI.
Review
Biochemistry & Molecular Biology
Nashwa El Hadidy, Vladimir N. Uversky, Xingmin Sun
Summary: This paper offers an overall review of the structural and functional differences between major toxins TcdA and TcdB of C. difficile, and suggests that intrinsic disorder may play a role in their pathogenic mechanisms.
CURRENT PROTEIN & PEPTIDE SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Aria Aminzadeh, Christian Engelbrecht Larsen, Thomas Boesen, Rene Jorgensen
Summary: Clostridioides difficile infections are the leading cause of healthcare-associated infectious diarrhea, mainly due to the virulence factors TcdA and TcdB. The structure of TcdA reveals dynamic movements and interactions that provide insights into its mechanism of action.
Article
Immunology
Caixia Tan, Fei Zhu, Yuanyuan Xiao, Yuqi Wu, Xiujuan Meng, Sidi Liu, Ting Liu, Siyao Chen, Juan Zhou, Chunhui Li, Anhua Wu
Summary: In this study, a multi-epitope vaccine against Clostridium difficile was designed using computer methods. The vaccine was able to induce immune response against both spore and propagule forms of the pathogen. The structure of the vaccine was predicted and validated, and its interaction with immune receptors was analyzed through docking and simulation. The findings suggest that the formulated vaccine shows promise against C. difficile, but further research is needed for verification.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Jason L. Larabee, D. Annie Doyle, Ummey Khalecha Bintha Ahmed, Tyler M. Shadid, Rachel R. Sharp, Kenneth L. Jones, Young Mi Kim, Shibo Li, Jimmy D. Ballard
Summary: Estrogen and Hippo signaling pathways independently regulate CSPG4 expression, and a small molecule inhibitor of Hippo signaling can protect against C. difficile infection by reducing CSPG4 expression. These findings provide significant insights into the regulation of CSPG4 expression and the potential therapeutic strategies for C. difficile disease.
Article
Chemistry, Physical
Agnieszka Sulowska, Izabela Wysocka, Daniel Pelczarski, Jakub Karczewski, Anna Zielinska-Jurek
Article
Chemistry, Physical
Konrad Trzcinski, Mariusz Szkoda, Maria Gazda, Jakub Karczewski, Adam Cenian, Galina M. Grigorian, Miroslaw Sawczak
Article
Chemistry, Physical
Karolina Cysewska, Maria Krystyna Rybarczyk, Grzegorz Cempura, Jakub Karczewski, Marcin Lapinski, Piotr Jasinski, Sebastian Molin
Article
Geochemistry & Geophysics
Michal Mierczak, Jerzy Karczewski
Summary: The article discusses the use of GPR method to locate agate geodes in Simota gully. With advanced signal processing procedures, several agate geodes were successfully excavated based on interpretation of the results.
Article
Chemistry, Multidisciplinary
Jakub Wawrzyniak, Jakub Karczewski, Emerson Coy, Igor Iatsunskyi, Jacek Ryl, Maria Gazda, Katarzyna Grochowska, Katarzyna Siuzdak
Summary: Selective laser-induced modification of nickel-decorated titania nanotubes enhances oxygen evolution reaction. The modified titania photoanode shows significantly higher donor concentration compared to the primary substrate, improving light-driven water splitting efficiency.
ADVANCED MATERIALS INTERFACES
(2021)
Article
Chemistry, Physical
Natalia Anna Wojcik, Sharafat Ali, Jakub Lech Karczewski, Bo Jonson, Michal Bartmanski, Ryszard Jan Barczynski
Summary: The study investigated the effects of replacing Na2O with MgO on the electrical, biosolubility, and thermal properties of bioactive glasses. The results showed that the DC conductivity of the glasses decreased after MgO substitution, and the ion conduction mechanism mainly involved ion hopping. In terms of biosolubility, the addition of magnesium improved the dissolution rate of the glasses and supported the formation of CaP-rich layers on the surface.
Article
Green & Sustainable Science & Technology
Agnieszka Piotrowska-Kirschling, Katarzyna Szelagowska-Rudzka, Jakub Karczewski, Joanna Brzeska
Summary: The study synthesized polyurethane-chitosan foams using chitosan obtained from shrimp shells, finding that the amount of Ch added affected the foam's properties, with 1.5% Ch resulting in the highest water and oil sorption. The SWOT analysis assessed the potential ecological value of the tested material as an innovative product.
Article
Engineering, Chemical
Agnieszka Piotrowska-Kirschling, Adam Olszewski, Jakub Karczewski, Lukasz Piszczyk, Joanna Brzeska
Summary: This research focused on utilizing shrimp waste to obtain chitosan for synthesizing chitosan-based polyurethane foams with different concentrations of chitosan. The addition of chitosan influenced the physicochemical characteristics and properties of the tested materials, with 1-3 wt% chitosan foams being softer than neat polyurethane.
Article
Zoology
A. Dobrzycka-Krahel, L. Rolbiecki, J. Karczewski, M. E. Skora
Summary: This study reports the distribution of epibiotic ciliates on signal crayfish for the first time and reveals that the presence of epibionts is determined by the morphology of the crayfish's exoskeleton. Smooth and regularly setae-covered surfaces show no epibionts, while dimpled surfaces with regular micro-papillae exhibit a new self-cleaning design.
JOURNAL OF ZOOLOGY
(2022)
Article
Nanoscience & Nanotechnology
Jakub Wawrzyniak, Jakub Karczewski, Emerson Coy, Jacek Ryl, Katarzyna Grochowska, Katarzyna Siuzdak
Summary: Although hydrogen is considered the green fuel of the future, its current production method is not environmentally friendly. Therefore, the development of efficient electrodes for hydrogen and oxygen production is crucial. This study employed laser-based modification technique to treat nanotubes containing transition metal species, and found that the laser treatment had opposite effects on hydrogen and oxygen evolution reactions. Structural and chemical analysis provided insights for more efficient, low-temperature water splitting.
Article
Chemistry, Physical
Marta Kowalkinska, Agnieszka Fiszka Borzyszkowska, Anna Grzegorska, Jakub Karczewski, Pawel Gluchowski, Marcin Lapinski, Miroslaw Sawczak, Anna Zielinska-Jurek
Summary: In this study, a novel WO3/S-doped g-C3N4 nanocomposite was developed for efficient removal of NOx in the air through photocatalytic reactions. The photocatalytic tests were conducted in a continuous-flow photoreactor, which demonstrated that the composite exhibited high efficiency in converting NO2 and had good stability.
Article
Polymer Science
Joanna Brzeska, Grzegorz Jasik, Wanda Sikorska, Barbara Mendrek, Jakub Karczewski, Marek Kowalczuk, Maria Rutkowska
Summary: This paper presents the results of testing the susceptibility to degradation in soil of branched polyesterurethane (PUR) based on poly([R,S]-3-hydroxybutyrate) (R,S-PHB), modified with poly([D,L]-lactide) (PLA) and starch (St). The study found that these materials underwent enzymatic degradation caused by microorganisms in the soil, resulting in changes in surface morphology while having minimal changes in molecular weight, chemical structure, and thermal properties.
Article
Chemistry, Physical
Agnieszka Fiszka Borzyszkowska, Agnieszka Sulowska, Ivar Zekker, Jakub Karczewski, Kai Bester, Anna Zielinska-Jurek
Summary: In this study, a novel Fe-ZnO/citric acid-modified cellulose composite was synthesized and characterized, and the photocatalytic degradation of IBU by different Fe and CAC content photocatalysts was investigated. The 0.5%Fe-ZnO-40%CAC catalyst exhibited high photocatalytic activity, and the addition of H2O2 significantly enhanced the degradation rate of IBU.
Article
Chemistry, Physical
Aleksander Mrozinski, Sebastian Molin, Patryk Blaszczak, Tadeusz Miruszewski, Karolina Gornicka, Jakub Karczewski, Piotr Jasinski
Summary: This work presents a comprehensive study on the impact of A-site non-stoichiometry on the physico-chemical properties of SrxTi0.3Fe0.7O3-d ceramics. The study includes structural analysis, evaluation of sintering and thermal expansion properties, determination of electrical properties, and fuel cell tests. The results show a dependence of the materials' properties on A-site non-stoichiometry.
INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
(2023)
Article
Engineering, Biomedical
Lukasz Pawlowski, Michal Bartmanski, Anna Ronowska, Adrianna Banach-Kopec, Szymon Mania, Bartlomiej Michal Cieslik, Aleksandra Mielewczyk-Gryn, Jakub Karczewski, Andrzej Zielinski
Summary: This study developed a novel titanium implant with high osteointegration properties and antimicrobial activity through surface modification. The multi-step modification process involved electrochemical oxidation, silver nanoparticle decoration, and biopolymer coating. The modified samples showed increased roughness, reduced burst release of silver, potent antimicrobial activity, and good compatibility with osteoblast cells.
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
(2023)