Article
Microbiology
Greg Hussack, Martin A. Rossotti, Henk van Faassen, Tomohiko Murase, Luiz Eugenio, Joseph D. Schrag, Kenneth K. -S. Ng, Jamshid Tanha
Summary: Crystal structures of camelid heavy-chain antibody variable domains (V(H)Hs) bound to fragments of the combined repetitive oligopeptides domain of Clostridiodes difficile toxin A (TcdA) revealed a spatial arrangement between VHH A20 and VHH A26. Based on this observation, a biparatopic fusion protein A20-A26 was generated, which showed improved binding affinity and neutralization potency compared to unfused A20 and A26 V(H)Hs. A20-A26 demonstrated higher potency than various control constructs. Size-exclusion chromatography-multiangle light scattering (SEC-MALS) analysis confirmed the 1:1 stoichiometry and simultaneous engagement of both A20 and A26 epitopes by A20-A26, in contrast to the varied and heterogeneous binding modes of control constructs. These results underscore the importance of molecular geometric constraints in generating highly potent antibody-based reagents.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Immunology
Hari P. Dulal, David J. Vance, Durga P. Neupane, Xiangcheng Chen, Jacqueline M. Tremblay, Charles B. Shoemaker, Nicholas J. Mantis, Jeongmin Song
Summary: Researchers generated a VHH antibody library from typhoid toxoid-immunized alpacas and identified six potent antibodies that can neutralize typhoid toxin and protect mice from its toxicity.
INFECTION AND IMMUNITY
(2022)
Article
Food Science & Technology
Selene Mogavero, Sarah Hoefs, Alexa N. Lauer, Rita Mueller, Sascha Brunke, Stefanie Allert, Franziska Gerwien, Sabrina Groth, Edward Dolk, Duncan Wilson, Thomas Gutsmann, Bernhard Hube
Summary: Candidalysin, a peptide toxin produced by Candida albicans, is identified as the hemolytic factor of the organism. Its hemolytic activity is regulated by the P7 peptide. The purinergic receptor antagonist PPADS can neutralize the hemolytic effect of candidalysin and also affects its membrane intercalation ability. Antibodies targeting candidalysin show potential for neutralization and future anti-Candida therapy.
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
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
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
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
Infectious Diseases
Sean Lee, Neha Nanda, Kenichiro Yamaguchi, Yelim Lee, Rosemary C. She
Summary: This study investigated the validity of using toxin B PCR cycle threshold (tcdB C-t) as a rapid and accurate method for detecting Clostridioides difficile toxin. The findings suggest that very low C-t values may have limited value in predicting positive toxin status using the cell cytotoxin neutralization assay (CCNA). Additional data are needed to support the use of C-t values in clinical laboratory reporting.
Article
Infectious Diseases
Miad Elahi, Haruyuki Nakayama-Imaohji, Masahito Hashimoto, Ayano Tada, Hisashi Yamasaki, Tamiko Nagao, Tomomi Kuwahara
Summary: The gut symbiont Bacteroides thetaiotaomicron (BT) suppresses Clostridium difficile (CD) toxin production by inhibiting polysaccharide metabolism pathways. Polysaccharide fractions derived from BT can suppress CD toxin production, with cell wall-associated glycans playing a key role in this inhibitory effect.
Review
Biochemistry & Molecular Biology
Dinendra L. Abeyawardhane, Raquel Godoy-Ruiz, Kaylin A. Adipietro, Kristen M. Varney, Richard R. Rustandi, Edwin Pozharski, David J. Weber
Summary: There is currently no treatment available for toxicities caused by Clostridioides difficile binary toxin, and new therapeutic strategies are needed to address this issue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Public, Environmental & Occupational Health
Peng An Khun, Thomas V. Riley
Summary: This review provides an overview of Clostridium difficile infection (CDI) in southeast Asia, including its prevalence, detection methods, antimicrobial susceptibility profiles, and the potential significance of a One Health approach. CDI is a common cause of hospital-acquired gastroenteritis worldwide, with higher rates observed in high-income countries. Lack of knowledge and awareness about CDI, along with antimicrobial abuse and inadequate education on appropriate usage, contribute to its evolution. Underreporting of CDI rates and misuse of antimicrobial agents pose a significant threat in regions like Indochina, while C. difficile RT 017 strain is endemic in southeast Asia.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2022)
Article
Microbiology
Mahmoud Fayez, Waleed R. El-Ghareeb, Ahmed Elmoslemany, Saleem J. Alsunaini, Mohamed Alkafafy, Othman M. Alzahrani, Samy F. Mahmoud, Ibrahim Elsohaby
Summary: The study investigated the presence of Clostridium perfringens and Clostridioides difficile in camel minced meat samples collected from small butcher shops and supermarkets in Al-Ahsa Governorate, Saudi Arabia. It was found that most isolates exhibited resistance to at least one antimicrobial, with some showing multidrug resistance. This highlights the importance of enforcing food safety standards and conducting regular inspections in abattoirs, small butcher shops, and supermarkets.
Article
Immunology
Bruce D. Wines, Liriye Kurtovic, Halina M. Trist, Sandra Esparon, Ester Lopez, Klasina Chappin, Li-Jin Chan, Francesca L. Mordant, Wen Shi Lee, Nicholas A. Gherardin, Sheila K. Patel, Gemma E. Hartley, Phillip Pymm, James P. Cooney, James G. Beeson, Dale Godfrey, Louise M. Burrell, Menno C. van Zelm, Adam K. Wheatley, Amy W. Chung, Wai-Hong Tham, Kanta Subbarao, Stephen J. Kent, P. Mark Hogarth
Summary: Joining a function-enhanced Fc-portion of human IgG to the SARS-CoV-2 entry receptor ACE2 produces an antiviral decoy with strain transcending virus neutralizing activity. Fc-modification was utilized to optimize SARS-CoV-2 neutralization and Fc-effector functions of ACE2-Fc decoy proteins. Different Fc-modifications had distinct effects on neutralization and effector functions.
FRONTIERS IN IMMUNOLOGY
(2022)
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
Pharmacology & Pharmacy
Tania Maria Manieri, Daniela Yumi Takata, Roselaine Campos Targino, Wagner Quintilio, Joao Victor Batalha-Carvalho, Camila Maria Lucia da Silva, Ana Maria Moro
Summary: This study identified a panel of neutralizing monoclonal antibodies (mAbs) against tetanus toxin (TeNT), some of which can neutralize the toxin and prevent symptoms and death in mice. Two mAbs were found to impair the binding of TeNT to the GT1b ganglioside receptor. Stable cell lines were generated to produce large quantities of mAbs, and their characteristics were analyzed.
