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
Multidisciplinary Sciences
Ashleigh S. Paparella, Briana L. Aboulache, Rajesh K. Harijan, Kathryn S. Potts, Peter C. Tyler, Vern L. Schramm
Summary: Clostridium difficile produces toxins TcdA and TcdB causing diarrhea by affecting host cell functions using UDP-glucose, leading to disease onset. Researchers identified potential therapeutic approach using transition state analogue iminosugars.
NATURE COMMUNICATIONS
(2021)
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
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
Microbiology
Marta Mattana, Riccardo Tomasello, Claudia Cammarata, Paola Di Carlo, Teresa Fasciana, Giulio Giordano, Alessandro Lucchesi, Sergio Siragusa, Mariasanta Napolitano
Summary: This review analyzed the correlation between coagulation complications related to C. difficile infection and inflammasome activation, particularly the pyrin-dependent one. The evidence suggests that inflammasome activation increases the risk of venous thromboembolism, and inhibition of molecules involved in coagulation activation could block this process. It may be possible to reduce complications and mortality associated with C. difficile infection by reducing inflammatory activity and preventing thromboembolic complications.
Article
Microbiology
Yingxue Li, Wei Xu, Yutian Ren, Hung-Chi Cheung, Panpan Huang, Guneet Kaur, Chih-Jung Kuo, Sean P. McDonough, Susan L. Fubini, Stephen M. Lipkin, Xin Deng, Yung-Fu Chang, Linfeng Huang
Summary: Clostridioides difficile infection is the leading cause of hospital-acquired diarrhea, and TcdB toxin can induce epithelial cell apoptosis through a yet unclear mechanism. Through an RNA interference screen, JUP protein and HMGB1 protein were identified as novel host factors involved in TcdB-induced cell apoptosis. JUP protein targets mitochondria and increases mitochondrial membrane permeability, promoting cell apoptosis.
Review
Medicine, General & Internal
Gowthami Sai Kogilathota Jagirdhar, Salim Surani
Summary: Pseudomembranous colitis is a severe inflammation of the colon caused by various factors, with Clostridium difficile being the most common cause. Symptoms include abdominal pain, diarrhea, fever, and dehydration. Other than C. difficile, other pathogens, medications, and diseases should be considered as differential diagnoses. Complications can be serious, and early diagnosis and treatment are crucial.
WORLD JOURNAL OF CLINICAL CASES
(2023)
Article
Pharmacology & Pharmacy
Giuseppe Esposito, Chiara Corpetti, Marcella Pesce, Luisa Seguella, Giuseppe Annunziata, Alessandro Del Re, Martina Vincenzi, Roberta Lattanzi, Jie Lu, Walter Sanseverino, Giovanni Sarnelli
Summary: The newly designed PEA-producing probiotic showed therapeutic potential in inhibiting colonic inflammation and restoring tight junction protein expression in a mouse model of CDI.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Nehad Ahmed, Ahmad Alamer, Ziyad Almalki, Ahmed Alshehri, Abdullah Alahmari
Summary: Clostridium difficile is the most common pathogen causing healthcare-associated diarrhea, and its primary risk factor is antibiotic exposure. Analysis of reports in the FAERS database reveals commonly reported drugs associated with drug-induced C. difficile infection.
LATIN AMERICAN JOURNAL OF PHARMACY
(2022)
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
Biochemistry & Molecular Biology
Prerana Sarangi, Lilesh Kumar Pradhan, Pradyumna Kumar Sahoo, Nishant Ranjan Chauhan, Saroj Kumar Das
Summary: The contamination of life-sustaining environments with synthetic pollutants, such as di-2-ethylhexyl phthalate (DEHP), has increased at an alarming rate. DEHP, commonly found in plastics, can cause reproductive toxicity, disrupt the thyroid endocrine system, and induce oxidative stress and neurodevelopmental defects. This study focused on the neurobehavioral effects of DEHP on zebrafish and found that it acts as a neurotoxicant by inducing oxidative stress and altering the glutathione biosynthetic pathway. Chronic exposure to DEHP also resulted in neuronal pyknosis and chromatin condensation in the zebrafish brain. Overall, the study suggests the potential role of DEHP in inducing neuropathological manifestations and highlights the need for further research on the neuroprotective efficacy of natural compounds.
FISH PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Lia M. Pinto, Alexandros Pailas, Max Bondarchenko, Abhishek Bharadwaj Sharma, Katrin Neumann, Anthony J. Rizzo, Celine Jeanty, Nathalie Nicot, Carine Racca, Mindy K. Graham, Catherine Naughton, Yaqun Liu, Chun-Long Chen, Paul J. Meakin, Nick Gilbert, Sebastien Britton, Alan K. Meeker, Christopher M. Heaphy, Florence Larminat, Eric Van Dyck
Summary: Maintaining chromatin integrity at centromeres is crucial for preventing DNA breaks and genomic instability. The histone chaperone complex ATRX/DAXX is involved in establishing and maintaining centromeric chromatin structure. We discovered a novel ATRX-independent function for DAXX in promoting genome stability by preventing R-loop accumulation and DNA double-strand break formation at centromeres.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Immunology
Deiziane V. S. Costa, Jae H. Shin, Sophia M. Goldbeck, David T. Bolick, Flavio S. Mesquita, Andrea V. Loureiro, Monica J. Rodrigues-Jesus, Gerly A. C. Brito, Cirle A. Warren
Summary: Increased risk of intestinal dysfunction has been reported in patients after Clostridioides difficile infection (CDI). Enteric glial cells (EGCs), a component of the enteric nervous system (ENS), contribute to gut homeostasis. Previous studies showed that adenosine receptors, A2A and A2B, modulate inflammation during CDI.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dong Kyu Kim, Hyobin Jeong, Jingi Bae, Moon-Yong Cha, Moonkyung Kang, Dongjin Shin, Shinwon Ha, Seung Jae Hyeon, Hokeun Kim, Kyujin Suh, Mi-Sun Choi, Hoon Ryu, Seong-Woon Yu, Jong-Il Kim, Yeon-Soo Kim, Sang-Won Lee, Daehee Hwang, Inhee Mook-Jung
Summary: This study reveals the crucial role of mitochondria in neural progenitors and their association with the protein amyloid-beta, which is linked to Alzheimer's disease. Mitochondrial dysfunction inhibits neuronal differentiation, leading to deficits in adult hippocampal neurogenesis and cognitive function. The research suggests that lysine demethylase 5A epigenetically suppresses differentiation in response to mitochondrial damage.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)