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)
Review
Gastroenterology & Hepatology
Salvador Lopez-Cardenas, Eva Torres-Martos, Juan Mora-Delgado, Juan Manuel Sanchez-Calvo, Marta Santos-Pena, Angel Zapata Lopez, Maria Dolores Lopez-Prieto, Salvador Perez-Cortes, Juan Carlos Alados
Summary: The study revealed that patients with detected presence of TcdB and CDT in feces exhibited greater disease severity and higher recurrence rates compared to those without detection. Simultaneous detection of both markers had a stronger impact on prognosis in cases of 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
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
Medicine, General & Internal
Andrew M. Skinner, S. Tyler Phillips, Michelle M. Merrigan, Kevin J. O'Leary, Susan P. Sambol, Farida Siddiqui, Lance R. Peterson, Dale N. Gerding, Stuart Johnson
Summary: Most pathogenic strains of C. difficile possess two large molecular weight single unit toxins that disrupt the actin cytoskeleton of intestinal epithelial cells, leading to diarrhea. While TcdB alone can cause disease, TcdA-/TcdB+ mutant strains have been shown to be responsible for C. difficile infection, which are typically mild in nature.
JOURNAL OF CLINICAL MEDICINE
(2021)
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.
Article
Oncology
Julia L. Drewes, Jie Chen, Nicholas O. Markham, Reece J. Knippel, Jada C. Domingue, Ada J. Tam, June L. Chan, Lana Kim, Madison McMann, Courtney Stevens, Christine M. Dejea, Sarah Tomkovich, John Michel, James R. White, Fuad Mohammad, Victoria L. Campodonico, Cody N. Heiser, Xinqun Wu, Shaoguang Wu, Hua Ding, Patricia Simner, Karen Carroll, Martha J. Shrubsole, Robert A. Anders, Seth T. Walk, Christian Jobin, Fengyi Wan, Robert J. Coffey, Franck Housseau, Ken S. Lau, Cynthia L. Sears
Summary: This study reveals the role of toxigenic Clostridioides difficile in promoting colorectal cancer, suggesting that chronic colonization with this pathogenic bacteria may drive tumor development through the induction of Wnt signaling, reactive oxygen species, and protumorigenic mucosal immune responses.
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
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
Microbiology
Zohar Hamo, Maya Azrad, Boris Fichtman, Avi Peretz
Summary: Different strains of Clostridioides difficile produce varying levels of toxins that have different degrees of damage to host cells. However, no direct association was found between specific bacterial strains, toxin concentrations, and disease severity.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Food Science & Technology
Masahiro Nagahama, Keiko Kobayashi, Sadayuki Ochi, Masaya Takehara
Summary: Clostridium botulinum C2 toxin requires lysosomal enzyme cathepsin B (CTSB) for effective cellular entry, with cysteine protease and aspartyl protease having different effects on cell rounding and extracellular ASMase activity induced by C2 toxin.
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
Cell Biology
Hung Chan, Qing Li, Xiansong Wang, Wing Yingzhi Liu, Wei Hu, Judeng Zeng, Chuan Xie, Thomas Ngai Yeung Kwong, Idy Hiu Ting Ho, Xiaodong Liu, Huarong Chen, Jun Yu, Ho Ko, Raphael Chiu Yeung Chan, Margaret Ip, Tony Gin, Alfred Sze Lok Cheng, Lin Zhang, Matthew Tak Vai Chan, Sunny Hei Wong, William Ka Kei Wu
Summary: Clostridioides difficile infection (CDI) is a common cause of nosocomial diarrhea. TcdB impairs lysosomal function in macrophages, leading to inflammation. Vitamin D-3 and carbamazepine protect against CDI by restoring lysosomal function and the expression of the transcription factor MITF in macrophages.
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
Chemistry, Analytical
Yuefan Wang, Yingwei Hu, Naseruddin Hoti, Lan Huang, Hui Zhang
Summary: The study introduces a method to preserve protein complexes by in vivo cross-linking, followed by size exclusion chromatography and data-independent acquisition mass spectrometry, enabling the characterization of in vivo protein complexes from cells or tissues to determine their clinical importance. This approach can identify protein complexes not detected by the in vitro system, providing unique insights into protein functions.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Clinton Yu, Xiaorong Wang, Lan Huang
Summary: Cross-linking mass spectrometry has advanced significantly as a technology for studying protein-protein interactions and protein complex architectures. Targeted QXL-MS platforms, such as PRM-based approaches, allow for label-free comparative analysis of selected cross-links across multiple samples.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Peng Chen, Rongsheng Jin
Summary: This article reviews recent research progress on the molecular mechanisms by which the Clostridioides difficile exotoxin TcdB recognizes Frizzed proteins (FZDs) and chondroitin sulfate proteoglycan 4 (CSPG4) as two major host receptors. The authors suggest that the receptor-binding sites and neutralizing epitopes on TcdB are ideal targets for the development of broad-spectrum inhibitors against various TcdB variants.
Article
Microbiology
Kwok-ho Lam, Jacqueline M. Tremblay, Kay Perry, Konstantin Ichtchenko, Charles B. Shoemaker, Rongsheng Jin
Summary: This study reports the identification and characterization of a large panel of new single-domain variable heavy-chain (VHH) antibodies that bind to the catalytic light chain (LC) of botulinum neurotoxins (BoNTs) and inhibit their protease activity. The researchers used a combination of X-ray crystallography and biochemical assays to investigate the structures and inhibition mechanisms of these VHHs, and found that they interact with the LC through diverse mechanisms and exhibit broad specificity. These findings are of great importance for the development of improved botulism therapeutics.
Article
Multidisciplinary Sciences
Baohua Chen, Zheng Liu, Kay Perry, Rongsheng Jin
Summary: The study reveals the mechanism of how toxin A from Clostridioides difficile causes diarrhea by glucosylating and inactivating Rho and Ras family small GTPases, providing insights into substrate recognition.
SCIENTIFIC REPORTS
(2022)
Correction
Cell Biology
Sohail Jahid, Jose A. Ortega, Linh M. Vuong, Isabella Maria Acquistapace, Stephanie J. Hachey, Jessica L. Flesher, Maria Antonietta La Serra, Nicoletta Brindani, Giuseppina La Sala, Jacopo Manigrasso, Jose M. Arencibia, Sine Mandrup Bertozzi, Maria Summa, Rosalia Bertorelli, Andrea Armirotti, Rongsheng Jin, Zheng Liu, Chi-Fen Chen, Robert Edwards, Christopher C. W. Hughes, Marco De Vivo, Anand K. Ganesan
Article
Cell Biology
Sohail Jahid, Jose A. Ortega, Linh M. Vuong, Isabella Maria Acquistapace, Stephanie J. Hachey, Jessica L. Flesher, Maria Antonietta La Serra, Nicoletta Brindani, Giuseppina La Sala, Jacopo Manigrasso, Jose M. Arencibia, Sine Mandrup Bertozzi, Maria Summa, Rosalia Bertorelli, Andrea Armirotti, Rongsheng Jin, Zheng Liu, Chi-Fen Chen, Robert Edwards, Christopher C. W. Hughes, Marco De Vivo, Anand K. Ganesan
Summary: CDC42 family GTPases control tumor cell invasion and angiogenesis, and a new drug called ARN22089 has been discovered to inhibit tumor growth and angiogenesis by modulating CDC42 signaling.
Article
Biology
Baohua Chen, Sujit Basak, Peng Chen, Changcheng Zhang, Kay Perry, Songhai Tian, Clinton Yu, Min Dong, Lan Huang, Mark E. Bowen, Rongsheng Jin
Summary: This study reports the crystal structure of Clostridioides difficile toxin A (TcdA), revealing its dynamic structure and pH-dependency. The study also identifies a small globular subdomain and the CROPs domain that protect the pore-forming region of TcdA at neutral pH. Furthermore, a rationally designed mutation drastically reduces the cytotoxicity of the toxin.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Rafael Alcala-Torano, Mariha Islam, Jaclyn Cika, Kwok Ho Lam, Rongsheng Jin, Konstantin Ichtchenko, Charles B. Shoemaker, James A. Van Deventer
Summary: This study successfully utilized yeast display in combination with noncanonical amino acids to identify irreversible variants of single-domain antibodies that can bind to botulinum neurotoxin light chain A. Systematic evaluations revealed clones with retained binding function and site-dependent target specificity and crosslinking capabilities conferred by the noncanonical amino acids.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Analytical
Fenglong Jiao, Leah J. Salituro, Clinton Yu, Craig B. Gutierrez, Scott D. Rychnovsky, Lan Huang
Summary: The development of MS-cleavable cross-linking mass spectrometry (XL-MS) allows for the efficient capture and identification of endogenous protein-protein interactions (PPIs) without the need for cell engineering. However, existing lysine-reactive cross-linkers have limitations in uncovering the complete PPI map. In this study, a sulfoxide-containing MS-cleavable haloacetamide-based cross-linker, DBrASO, was designed and synthesized to complement lysine-reactive reagents and expand PPI coverage at a systems-level.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Linfeng Gao, Kwok-ho Lam, Shun Liu, Adina Przykopanski, Johanna Luebke, Ruifeng Qi, Maren Krueger, Maria B. Nowakowska, Katja Selby, Francois P. Douillard, Martin B. Dorner, Kay Perry, Miia Lindstrom, Brigitte G. Dorner, Andreas Rummel, Rongsheng Jin
Summary: This article reports the crystal structures of OrfX1, OrfX2, and an OrfX1-OrfX3 complex encoded in the orfX cluster, which lays the foundation for future studies on the potential roles of OrfX proteins in oral intoxication and pathogenesis of BoNTs.
Article
Multidisciplinary Sciences
Songhai Tian, Xiaozhe Xiong, Ji Zeng, Siyu Wang, Benjamin Jean-Marie Tremblay, Peng Chen, Baohua Chen, Min Liu, Pengsheng Chen, Kuanwei Sheng, Daniel Zeve, Wanshu Qi, David T. Breault, Cesar Rodriguez, Ralf Gerhard, Rongsheng Jin, Andrew C. Doxey, Min Dong
Summary: Toxin B (TcdB) is a major exotoxin responsible for diseases associated with Clostridioides difficile infection. This study identifies tissue factor pathway inhibitor (TFPI) as a host receptor for TcdB4 and TcdB10 subtypes, and reveals intragenic micro-recombination (IR)-driven changes on receptor specificity among TcdB variants.
NATURE COMMUNICATIONS
(2022)
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
Biophysics
Bright Shi, Tsutomu Matsui, Shuo Qian, Thomas M. Weiss, Iain D. Nicholl, David J. E. Callaway, Zimei Bu
Summary: The cell-cell adhesion cadherin-catenin complexes recruit vinculin to the adherens junction (AJ), but the specific influence of vinculin on AJ structure and function remains unclear. This study identifies two patches of salt bridges that lock vinculin in an autoinhibited conformation and reconstitutes the vinculin activation mimetics bound to the cadherin-catenin complex. The dynamic cadherin-catenin-vinculin complex employs vinculin as the primary F-actin binding mode to strengthen AJ-cytoskeleton interactions.
BIOPHYSICAL JOURNAL
(2023)
