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
Meng Wang, Zifeng Deng, Yanmei Li, Yi Ma, Jufang Wang
Summary: A novel lytic protein Cw1-CWB2 with high binding specificity and strong lytic activity has been designed in this study for combating C. difficile.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(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
Immunology
Camila Fonseca Rizek, Roberta Cristina Martins, Evelyne Santana Girao, Bruno de Melo Tavares, Sania Alves Dos Santos, Gessica Lorena Gamarra, Lauro Vieira Perdigao Neto, Constancia Diogo, Tatiana D' Annibale Orsi, Icaro Boszczowski, Filipe Piastrelli, Cecilia Leite Costa, Daniely Viana Costa, Geovania Maciel, Janete Romao, Gerly Anne de Castro Brito, Silvia Figueiredo Costa
Summary: Clostridioides difficile (CD) is the most common cause of healthcare-related diarrhea, and its severity has increased due to the spread of hypervirulent strains. Toxin production is the most important virulence factor for CD, but other factors, such as adhesion-related genes, also contribute to its virulence.
MICROBES AND INFECTION
(2022)
Article
Microbiology
Shaohui Wang, Duolong Zhu, Xingmin Sun
Summary: In this study, immunodominant fragments of TcdA and TcdB (Tcd169) were expressed in a nontoxigenic C. difficile strain, generating a promising oral/mucosal vaccine candidate against CDI. Importantly, sera raised against Tcd169 protein showed significant cross-reactivity with FliC/FliD and two surface layer proteins (SlpA and Cwp2), which are involved in C. difficile adhesion/colonization. Oral immunizations with the vaccine candidate provided effective protection against C. difficile infection in mice.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Siqi Wang, Leyang Xiang, Fang li, Wenlin Deng, Pinjing Lv, Ye Chen
Summary: This study found that levels of fecal short-chain fatty acids (SCFAs), particularly butyrate, are reduced, and normal colon structure is damaged in patients with CDI compared with those in healthy individuals. Bile acid (BA) metabolic disorder in patients with CDI is characterized by increased primary BA levels and decreased secondary BAs. Butyrate treatment may serve as a novel therapeutic approach for patients with CDI.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biotechnology & Applied Microbiology
Jianfeng Wang, Chu Yang, Chao Zhang, Xiaoyan Mao, An Lizhe
Summary: In this study, the genome of Clostridium difficile was studied using metagenomic technology, revealing its gene sequence information and potential toxicological genes. Through gene function analysis and pathogenicity analysis, the metabolism activity, catalytic activity, carbohydrate-active enzyme genes and other aspects of the bacterium were understood, and an assessment was made on its virulence genes.
Article
Engineering, Environmental
Caitlin Courtney, Antoine Brison, Dyllon G. Randall
Summary: Stabilizing urine with calcium hydroxide can prevent enzymatic urea hydrolysis, allowing for maximum nitrogen recovery. Adding air and carbon dioxide to stabilized urine can effectively remove calcium ions as calcium carbonate, with air bubbling being the more cost-efficient option. The study found that calcium removal efficiency can reach up to 98% at certain air flow rates, and that even if the pH decreases, urine remains stabilized with no enzymatic urea hydrolysis.
Article
Biochemistry & Molecular Biology
Anukriti Mathur, Callum Kay, Yansong Xue, Abhimanu Pandey, Jiwon Lee, Weidong Jing, Daniel Enosi Tuipulotu, Jordan Lo Pilato, Shouya Feng, Chinh Ngo, Anyang Zhao, Cheng Shen, Melanie Rug, Lisa A. Miosge, Ines I. Atmosukarto, Jason D. Price, Sidra A. Ali, Elizabeth E. Gardiner, Avril A. B. Robertson, Milena M. Awad, Dena Lyras, Nadeem O. Kaakoush, Si Ming Man
Summary: Two virulence factors, lecithinase and perfringolysin O, from the human bacterial pathogen Clostridium perfringens, activate the NLRP3 inflammasome in mice and humans, inducing inflammation and cell death. Lecithinase enters vesicular structures and induces lysosomal membrane destabilization, leading to the release of inflammatory cytokines IL-1β and IL-18.
Article
Microbiology
Julie Gilbert, Jhansi Leslie, Rose Putler, Shayna Weiner, Alexandra Standke, Aline Penkevich, Micah Keidan, Vincent B. Young, Krishna Rao
Summary: This study found that detecting anti-toxin A antibodies in CDI patients was associated with an increased risk of recurrence, while the association was weaker for anti-toxin B antibodies. Adjusting for confounders weakened the relationship between anti-toxin A antibodies and recurrence, and sensitivity analyses confirmed the findings. Future studies are needed to investigate the association between neutralizing antibodies levels and recurrence post-treatment.
Review
Microbiology
Gabriela Muniz Carvalho, Carolina Pantuzza Ramos, Francisco Carlos Faria Lobato, Roberto Mauricio Carvalho Guedes, Paula Roberta Giaretta, Rodrigo Otavio Silveira Silva
Summary: There is a lack of published guidelines for the diagnosis of Clostridioides (Clostridium) difficile infection (CDI) in animals. The performance of available methods for detecting CDI varies among different animal species. Enzyme immunoassays have shown low performance in detecting toxins A and B in piglet and dog samples, while having high sensitivity for foals. Tests for detecting glutamate dehydrogenase (GDH) have been identified as a suitable screening method with high sensitivity in animal samples. Studies evaluating real-time PCR or nucleic acid amplification tests have shown low performance for detecting CDI in animals. Histopathology can be a useful tool for post-mortem diagnosis in animals with CDI.
Article
Multidisciplinary Sciences
Srijita Basak, Debashrito Deb, Utkarsh Narsaria, Tamalika Kar, Filippo Castiglione, Indraneel Sanyal, Pratap D. Bade, Anurag P. Srivastava
Summary: Clostridium difficile infection is a major health-associated infection with high incidence and mortality rates. A chimeric vaccine candidate was designed using immunoinformatics, which showed stability and reliability in silico and molecular dynamics simulations. Docking studies demonstrated stable interactions with immune receptors, and in silico modeling indicated competent expression in E. coli system for potential immune response.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Mao Hagihara, Tadashi Ariyoshi, Yasutoshi Kuroki, Shuhei Eguchi, Seiya Higashi, Takeshi Mori, Tsunemasa Nonogaki, Kenta Iwasaki, Makoto Yamashita, Nobuhiro Asai, Yusuke Koizumi, Kentaro Oka, Motomichi Takahashi, Yuka Yamagishi, Hiroshige Mikamo
Summary: CBM 588 enhances the antibacterial activity against C. difficile, reduces colon epithelial damage, and improves immunity through upregulating pathogen specific immunoglobulin A and enhancing gut epithelial barrier function to protect colon tissue from CDI.
SCIENTIFIC REPORTS
(2021)
Article
Food Science & Technology
Katharina Ernst, Marc Landenberger, Julian Nieland, Katharina Norgaard, Manfred Frick, Giorgio Fois, Roland Benz, Holger Barth
Summary: The study investigated the cytotoxic effect of CDTb on cells, revealing that CDTb impairs cell viability and leads to redistribution of F-actin without affecting tubulin structures in CaCo-2 cells. Pharmacological pore blockers were found to effectively inhibit the cytotoxicity induced by pore formation of CDTb in the cytoplasmic membrane.
Review
Immunology
Jessica E. Buddle, Robert P. Fagan
Summary: Clostridioides difficile is a common cause of hospital-associated diarrhea, with high recurrence, morbidity, and mortality rates. Antibiotics are both the main treatment and a major risk factor for infection. The increasing multidrug resistance of C. difficile poses an urgent threat to global health. This review focuses on the virulence factors, antimicrobial resistance, and genome plasticity that enable the pathogenesis and persistence of this important pathogen.