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
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
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
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
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
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
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.
Article
Multidisciplinary Sciences
Peng Chen, Ji Zeng, Zheng Liu, Hatim Thaker, Siyu Wang, Songhai Tian, Jie Zhang, Liang Tao, Craig B. Gutierrez, Li Xing, Ralf Gerhard, Lan Huang, Min Dong, Rongsheng Jin
Summary: Chondroitin sulfate proteoglycan 4 (CSPG4) is identified as a potential receptor for C. difficile toxin B (TcdB) during C. difficile infections (CDIs). The cryo-EM structure of a TcdB-CSPG4 complex and CDI mouse models offer insights into the role of CSPG4 in CDIs and suggest a therapeutic strategy targeting TcdB.
NATURE COMMUNICATIONS
(2021)
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
Multidisciplinary Sciences
Simoun Icho, Jennifer S. Ward, John Tam, Larry K. Kociolek, Casey M. Theriot, Roman A. Melnyk
Summary: This study investigated the impact of the total pool of intestinal bile acids on the virulence of Clostridioides difficile. It was found that the amount of bile acids in the intestine is correlated with the ability to inhibit TcdB toxicity. Even in antibiotic-treated and germ-free mice, bile acids were able to protect cells from TcdB damage, but this protection could be overcome at high toxin doses typical of severe infections. These findings reveal the role of intestinal bile acids in attenuating virulence and provide insights into asymptomatic carriage of toxigenic C. difficile, as well as strategies for manipulating bile acid levels for therapeutic benefit.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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
Biochemistry & Molecular Biology
Jinglue Song, Xia Shen, Zhenyu Huang, Yun Liu, Long Cui, Xuewei Cui, Chen-Ying Liu
Summary: Toxins A and B of Clostridium difficile disrupt the Hippo pathway, leading to sequestration and inactivation of YAP and TAZ in colonic epithelial cells. Overexpression of YAP restores cell function and may serve as a potential therapeutic strategy for treating CDI.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2021)
Article
Food Science & Technology
Nayra F. Q. R. Freitas, Denis Y. Otaka, Cleideanny C. Galvao, Dayane M. de Almeida, Marcos R. A. Ferreira, Clovis Moreira Junior, Marina M. M. H. Hidalgo, Fabricio R. Conceicao, Felipe M. Salvarani
Summary: The study immunized horses with recombinant proteins to prevent diseases caused by Clostridium perfringens, finding that 200 μg may be the ideal concentration, and antibody levels decreased after 60 days.
Article
Infectious Diseases
Martin J. Llewelyn, Detelina Grozeva, Philip Howard, Joanne Euden, Sarah M. Gerver, Russell Hope, Margaret Heginbothom, Neil Powell, Colin Richman, Dominick Shaw, Emma Thomas-Jones, Robert M. West, Enitan D. Carrol, Philip Pallmann, Jonathan A. T. Sandoe
Summary: Introduction of procalcitonin testing in emergency departments/acute medical units in England was associated with an initial decrease in antibiotic use per admission per week per trust, but this effect was not sustained over time. The introduction of procalcitonin testing in the ICU setting did not result in a significant change in antibiotic use. Further research is needed to determine the patient-level impact of procalcitonin testing and its potential clinical effectiveness.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Eric P. Budgell, Timothy J. Davies, Tjibbe Donker, Susan Hopkins, David H. Wyllie, Tim E. A. Peto, Martin J. Gill, Martin J. Llewelyn, A. Sarah Walker
Summary: There is no evidence that wide variation in hospital antibiotic use is associated with adjusted mortality risk in acute/general medicine inpatients. Using low-prescribing hospitals as benchmarks could help drive safe and substantial reductions in antibiotic consumption of up-to one-third in this population.
JOURNAL OF INFECTION
(2022)
Article
Medicine, General & Internal
Peter W. Horby, Guilherme Pessoa-Amorim, Natalie Staplin, Jonathan R. Emberson, Mark Campbell, Enti Spata, Leon Peto, Nigel J. Brunskill, Simon Tiberi, Victor Chew, Thomas Brown, Hasan Tahir, Beate Ebert, David Chadwick, Tony Whitehouse, Rahuldeb Sarkar, Clive Graham, J. Kenneth Baillie, Buddha Basnyat, Maya H. Buch, Lucy C. Chappell, Jeremy Day, Saul N. Faust, Raph L. Hamers, Thomas Jaki, Edmund Juszczak, Katie Jeffery, Wei Shen Lim, Alan Montgomery, Andrew Mumford, Kathryn Rowan, Guy Thwaites, Marion Mafham, Richard Haynes, Martin J. Landray
Summary: In patients hospitalized with COVID-19, aspirin was not associated with reductions in 28-day mortality or in the risk of progressing to invasive mechanical ventilation or death, but was associated with a small increase in the rate of being discharged alive within 28 days.
Article
Infectious Diseases
Johannes Camp, Tim Filla, Lina Glaubitz, Achim J. Kaasch, Frieder Fuchs, Matt Scarborough, Hong Bin Kim, Robert Tilley, Chun-Hsing Liao, Jonathan Edgeworth, Emmanuel Nsutebu, Luis Eduardo Lopez-Cortes, Laura Morata, Martin J. Llewelyn, Vance G. Fowler, Guy Thwaites, Harald Seifert, Winfried Kern, Siegbert Rieg
Summary: This study investigated the impact of neutropenia on the mortality and long-term outcomes of Staphylococcus aureus bloodstream infection. The results showed that neutropenia was not associated with a higher survival rate during follow-up, but neutropenic patients had a lower rate of SAB infection-related late complications.
CLINICAL MICROBIOLOGY AND INFECTION
(2022)
Article
Infectious Diseases
Francesc Escrihuela-Vidal, Achim J. Kaasch, Maja Von Cube, Siegbert Rieg, Winfried V. Kern, Harald Seifert, Kyoung-Ho Song, Chun-Hsing Liao, Robert Tilley, Hannah Gott, Matt Scarborough, Claire Gordon, Martin J. Llewelyn, Richard Kuehl, Laura Morata, Alex Soriano, Jonathan Edgeworth, Enrique Ruiz De Gopegui, Emmanuel Nsutebu, Jose Miguel Cisneros, Vance G. Fowler, Guy Thwaites, Joaquin Lopez-Contreras, Gavin Barlow, Hugo Guillermo Ternavasio-De La Vega, Jesus Rodriguez-Bano, Luis Eduardo Lopez-Cortes
Summary: This study analysed the adherence and impact of quality-of-care indicators (QCIs) in the management of Staphylococcus aureus bloodstream infection. The results showed that adherence to QCIs was associated with reduced 90-day mortality.
CLINICAL MICROBIOLOGY AND INFECTION
(2023)
Article
Public, Environmental & Occupational Health
Meghana Kamineni, Erkin Otles Meng, Jeeheh Oh, Krishna Rao, Vincent B. Young, Benjamin Y. Li, Lauren R. West, David C. Hooper, Erica S. Shenoy, John G. Guttag, Jenna Wiens, Maggie Makar
Summary: This article presents the prospective and retrospective evaluations of two CDI infection risk prediction models and discusses their robustness to data-set shifts.
INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Anna S. C. Conlon, Zoey Chopra, Shannon Cahalan, Sandro Cinti, Krishna Rao
Summary: This study aims to describe the natural course of procalcitonin (PCT) in COVID-19 patients and its correlation with antimicrobial prescribing, providing insights into PCT data utilization in antimicrobial stewardship. The results show that PCT trends are associated with antibiotic initiation and duration of treatment, independent of pneumonia status and comorbidities.
INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Felicia Kuperwaser, Gal Avital, Michelle J. Vaz, Kristen N. Noble, Allison N. Dammann, Tara M. Randis, David M. Aronoff, Adam J. Ratner, Itai Yanai
Summary: Group B Streptococcus (GBS) is a pathobiont that ascends to the placenta and causes adverse pregnancy outcomes by producing the toxin beta-hemolysin/cytolysin (beta-h/c). This study shows that GBS modulates the state of innate immune cells by subverting host inflammation through beta-h/c, leading to worse outcomes.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Review
Obstetrics & Gynecology
Malavika Prabhu, Gianna Wilkie, Mark MacEachern, Dana LaBuda, Jasmine Purtell, Krishna Rao, Laura E. E. Riley, Matthew Fuller, Morgan Rosser, Ashraf S. S. Habib, Melissa E. E. Bauer
Summary: The study aims to determine the mean procalcitonin levels in different groups of pregnant women and evaluate its usefulness in identifying infection.
INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
(2023)
Article
Multidisciplinary Sciences
Joshua Soto Ocana, Nile U. Bayard, Jessica L. Hart, Audrey K. Thomas, Emma E. Furth, D. Borden Lacy, David M. Aronoff, Joseph P. Zackular
Summary: Clostridioides difficile damages the colonic mucosa through potent exotoxins. The factors contributing to C. difficile pathogenesis are not fully understood, but likely involve ecological, immune, and environmental factors. Recent studies have shown that nonsteroidal anti-inflammatory drugs exacerbate C. difficile infection, although the mechanism behind this is unclear.
Article
Gastroenterology & Hepatology
Patricia P. Bloom, Krishna Rao, Christine Bassis, Borko Nojkov, Vincent B. Young, Anna S. F. Lok
Summary: Patients with cirrhosis have higher duodenal epithelial permeability and lower mucosal bacteria alpha diversity compared to controls, while no such differences are seen in the ileum or colon. Specific bacteria are associated with epithelial permeability and future hepatic decompensation.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Martin J. Llewelyn, Nicholas Price, Natasha Ratnaraja, Bridget Atkins, David Partridge, Katie Jeffery
Summary: The NHS in the UK witnessed a significant reduction in life-threatening community-acquired infections in its first two decades. However, advancements in medicine have brought new challenges such as antimicrobial resistance and healthcare-associated infections, particularly in an aging population. The COVID-19 pandemic has further highlighted the need for equal provision of NHS infection services across the country. This article recommends a comprehensive review and improvement in four key areas: creating a multidisciplinary specialty of infection medicine, streamlining infection training, establishing a national network of infectious diseases units, and standardizing the framework for integrated infection services at the local level.
Article
Medicine, General & Internal
Peter W. Horby, Jonathan R. Emberson, Marion Mafham, Mark Campbell, Leon Peto, Guilhenne Pessoa-Amorim, Enti Spata, Natalie Staplin, Catherine Lowe, David R. Chadwick, Christopher Brightling, Richard Stewart, Paul Collini, Abdul Ashish, Christopher A. Green, Ben Prudon, Timothy Felton, Anthony Kerry, J. Kenneth Baillie, Maya H. Such, Jeremy Day, Saul N. Faust, Thomas Jaki, Katie Jeffery, Edmund Juszczak, Marian Knight, Wei Shen Lim, Alan Montgomery, Andrew Mumford, Kathryn Rowan, Guy Thwaites, Richard Haynes, Martin J. Landray
Summary: This study evaluated the use of baricitinib in the treatment of patients hospitalized with COVID-19. The results showed that baricitinib significantly reduced the risk of death, although the effect size was slightly smaller than previous trials. Overall evidence suggests that JAK inhibitors can reduce mortality in hospitalized COVID-19 patients by about 20%.
Article
Medicine, General & Internal
Peter W. Horby, Marion Mafham, Leon Peto, Mark Campbell, Guilherme Pessoa-Amorim, Enti Spata, Natalie Staplin, Jonathan R. Emberson, Benjamin Prudon, Paul Hine, Thomas Brown, Christopher A. Green, Rahuldeb Sarkar, Purav Desai, Bryan Yates, Tom Bewick, Simon Tiberi, Tim Felton, J. Kenneth Baillie, Maya H. Bitch, Lucy C. Chappell, Saul N. Faust, Thomas Jaki, Katie Jeffery, Edmund Juszczak, Wei Shen Lim, Alan Montgomery, Andrew Mumford, Kathryn Rowan, David M. Weinreich, Richard Haynes, Martin J. Landray
Summary: This study evaluated the efficacy and safety of the combination therapy of casirivimab and imdevimab in patients hospitalized with COVID-19. The results showed that this combination therapy reduced the 28-day mortality rate in patients without detectable antibodies to SARS-CoV-2 infection at baseline, but not in those with detectable antibodies.
