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
Immunology
Colleen M. Pike, John Tam, Roman A. Melnyk, Casey M. Theriot
Summary: CDI is a highly inflammatory disease, and alternative therapies are needed. Conjugation of bile acids may have different therapeutic mechanisms against C. difficile and host during CDI.
INFECTION AND IMMUNITY
(2022)
Review
Gastroenterology & Hepatology
Andrea Martinez Aguirre, Joseph A. Sorg
Summary: Clostridioides difficile, a nosocomial pathogen, is a burden to the healthcare system. Disruption of the gut microbiome, commonly caused by broad-spectrum antibiotics, creates a susceptible state for CDI. Various metabolites produced by the host and/or gut microbiota interact with C. difficile, affecting its germination, growth, and colonization. Understanding the interactions between C. difficile and the host's gut microbiome and metabolites becomes more relevant as non-antibiotic CDI treatment advances.
Article
Microbiology
Nicole G. Metzendorf, Lena Melanie Lange, Nina Lainer, Rabea Schlueter, Silvia Dittmann, Lena-Sophie Paul, Daniel Troitzsch, Susanne Sievers
Summary: Clostridioides difficile, an anaerobic bacterium, is a problematic pathogen in hospitals, and dysbiosis decreases the resistance against it. In this study, the researchers investigated the effects of different bile acids on the bacterium and found that they could modify various virulence determinants, such as flagella expression, host cell adhesion, and toxin synthesis.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Alexander B. Smith, Matthew L. Jenior, Orlaith Keenan, Jessica L. Hart, Jonathan Specker, Arwa Abbas, Paula C. Rangel, Chao Di, Jamal Green, Katelyn A. Bustin, Jennifer A. Gaddy, Maribeth R. Nicholson, Clare Laut, Brendan J. Kelly, Megan L. Matthews, Daniel R. Evans, Daria Van Tyne, Emma E. Furth, Jason A. Papin, Frederic D. Bushman, Jessi Erlichman, Robert N. Baldassano, Michael A. Silverman, Gary M. Dunny, Boone M. Prentice, Eric P. Skaar, Joseph P. Zackular
Summary: Enterococci can shape the metabolic environment in the gut and enhance the fitness and pathogenesis of Clostridioides difficile through nutrient restriction and cross-feeding. This microbial interaction plays a role in the susceptibility to and the severity of C. difficile infection.
Review
Microbiology
Harish Chandra, Joseph A. Sorg, Daniel J. Hassett, Xingmin Sun
Summary: This review summarizes the current understanding of the transcription factors that regulate toxin production in Clostridioides difficile (CD). These transcription factors interconnect with pathways of flagellar synthesis, quorum sensing, motility, biofilm formation, sporulation, and phase variation, and are tightly linked to other cellular processes in CD.
CRITICAL REVIEWS IN MICROBIOLOGY
(2023)
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
Immunology
Cody P. Doolan, Thomas Louie, Christopher Lata, Oscar E. Larios, William Stokes, Joseph Kim, Kristen Brown, Paul Beck, Rob Deardon, Dylan R. Pillai
Summary: A study utilized latent class analysis (LCA) to determine the genuine probability of Clostridioides difficile infection (CDI) based on laboratory and clinical variables, establishing 3 CDI probability zones. The most fitting model incorporated toxigenic culture, clinical diagnosis, and toxin antigen detection. Commercial real-time PCR platforms could delineate CDI probability zones based on Ct values obtained from LCA results.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Gastroenterology & Hepatology
Anqi Jin, Tony Chien, Qiwen Huang, Pragati Kenkare, Mai Vu, Sandra Wilson, Edward S. Huang
Summary: The study found that cholecystectomy is associated with a slightly increased risk of incident CDI, but this effect is not influenced by the use of proton pump inhibitors, antibiotics, or hospitalization.
DIGESTIVE DISEASES AND SCIENCES
(2021)
Review
Gastroenterology & Hepatology
Mi Tang, Liling Xiong, Jianghui Cai, Jinzhu Fu, Hong Liu, Ying Ye, Li Yang, Shasha Xing, Xiao Yang
Summary: Intrahepatic cholestasis of pregnancy (ICP) is a common pregnancy-specific liver disease, and its etiology remains poorly understood. With the advancement of bioinformatics, the use of various omics techniques to study the pathogenesis and diagnosis and treatment direction of ICP has emerged.
HEPATOLOGY INTERNATIONAL
(2023)
Article
Immunology
Farhan Anwar, Bryan Angelo P. Roxas, Kareem W. Shehab, Neil M. Ampel, V. K. Viswanathan, Gayatri Vedantam
Summary: Clostridioides difficile is a major cause of healthcare-associated infections worldwide. A study on CDI diagnostic methods found a significant percentage of patients with discrepant test results, containing low-toxin strains that exhibited strong virulence in experiments.
EMERGING MICROBES & INFECTIONS
(2022)
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
Gastroenterology & Hepatology
Shanlin Ke, Nira R. Pollock, Xu-Wen Wang, Xinhua Chen, Kaitlyn Daugherty, Qianyun Lin, Hua Xu, Kevin W. Garey, Anne J. Gonzales-Luna, Ciaran P. Kelly, Yang-Yu Liu
Summary: The study highlights the sensitivity of interactions between gut microbiota and host immune markers to the status of C. difficile colonization and infection. Utilizing both types of data can improve the distinction between CDI and other groups. Symbolic classification using selected features resulted in simple mathematical formulas that explicitly quantify the interactions between the gut microbiome and host immune markers.
Article
Immunology
Nicholas O. Markham, Sarah C. Bloch, John A. Shupe, Erin N. Laubacher, Audrey K. Thomas, Heather K. Kroh, Kevin O. Childress, F. Christopher Peritore-Galve, M. Kay Washington, Robert J. Coffey, D. Borden Lacy
Summary: Clostridioides difficile is associated with nearly 225,000 antibiotic-associated diarrheal infections and almost 13,000 deaths per year in the United States. The intrarectal instillation mouse model with purified recombinant TcdA and TcdB provides flexibility to better understand structure/function relationships in different stages of CDI pathogenesis.
INFECTION AND IMMUNITY
(2021)
Article
Infectious Diseases
Supapit Wongkuna, Tavan Janvilisri, Matthew Phanchana, Phurt Harnvoravongchai, Amornrat Aroonnual, Sathid Aimjongjun, Natamon Malaisri, Surang Chankhamhaengdecha
Summary: Clostridioides difficile strains and patterns of antimicrobial resistance in Thailand show temporal changes in distribution and resistance.
Article
Microbiology
David M. Anderson, Michael J. Sheedlo, Jaime L. Jensen, D. Borden Lacy
NATURE MICROBIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Melissa A. Farrow, Nicole M. Chumber, Sarah C. Bloch, McKenzie King, Kaycei Moton-Melancon, John Shupe, Mary K. Washington, Benjamin W. Spiller, D. Borden Lacy
ACS CHEMICAL BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Michael J. Sheedlo, David M. Anderson, Audrey K. Thomas, D. Borden Lacy
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biology
Clarissa L. Durie, Michael J. Sheedlo, Jeong Min Chung, Brenda G. Byrne, Min Su, Thomas Knight, Michele Swanson, D. Borden Lacy, Melanie D. Ohi
Article
Biology
Michael J. Sheedlo, Jeong Min Chung, Neha Sawhney, Clarissa L. Durie, Timothy L. Cover, Melanie D. Ohi, D. Borden Lacy
Article
Genetics & Heredity
Sandra Janezic, Kate Dingle, Joseph Alvin, Tomaz Accetto, Xavier Didelot, Derrick W. Crook, D. Borden Lacy, Maja Rupnik
MICROBIAL GENOMICS
(2020)
Article
Immunology
Georgia C. Caso, Mark S. McClain, Amanda L. Erwin, Mandy D. Truelock, Anne M. Campbell, Catherine S. Leasure, Marcus Nagel, Kevin L. Schey, D. Borden Lacy, Melanie D. Ohi, Timothy L. Cover
Summary: The study investigates the mechanisms of VacA oligomerization and its activity, demonstrating that amino acid mutations and paired cysteine substitutions at interprotomer contact sites affect VacA assembly and function. Wild-type VacA oligomers disassemble under acidic pH, while mutant proteins with paired cysteine substitutions remain in an oligomeric state. The findings enhance our understanding of the molecular interactions required for VacA oligomerization and support a model where toxin activity depends on interactions with host cells.
INFECTION AND IMMUNITY
(2021)
Article
Biology
Michael J. Sheedlo, Clarissa L. Durie, Jeong Min Chung, Louise Chang, Jacquelyn Roberts, Michele Swanson, Dana Borden Lacy, Melanie D. Ohi
Summary: This passage discusses the relationship between Legionella pneumophila and Legionnaires' disease, as well as the structure of the Dot/Icm T4SS core complex determined by single particle cryo-EM. It identifies new proteins contributing to the core T4SS structure and defines two areas of symmetry mismatch.
Review
Microbiology
Shannon L. Kordus, Audrey K. Thomas, D. Borden Lacy
Summary: Clostridioides difficile produces up to three different toxins, which play a key role in the pathogenesis of colon infection. In this Review, Kordus, Thomas, and Lacy discuss the structure and function of these toxins and how this information guides new therapeutic approaches. Understanding the mechanisms of host-toxin interactions provides a foundation for developing novel strategies for the treatment and prevention of C. difficile infection.
NATURE REVIEWS MICROBIOLOGY
(2022)
Article
Microbiology
F. Christopher Peritore-Galve, John A. Shupe, Rory J. Cave, Kevin O. Childress, M. Kay Washington, Sarah A. Kuehne, D. Borden Lacy
Summary: Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea and pseudomembranous colitis in the USA. This study investigates the role of two protein toxins, TcdA and TcdB, produced by the pathogen in causing disease. The study finds that both toxins have an additive role in disease pathogenesis and produce both glucosyltransferase-dependent and independent phenotypes. These findings will contribute to the development of toxin-based therapeutics for CDI.
Article
Microbiology
Katie Saund, Ali Pirani, D. Borden Lacy, Philip C. Hanna, Evan Snitkin
Summary: In this study, it was demonstrated that genomic variants outside the pathogenicity locus (PaLoc) of Clostridioides difficile are associated with changes in cytotoxicity. Multiple approaches were used to provide evidence for this association. The study also highlighted the importance of genomic variation in determining various in vitro phenotypes crucial for clinical infection. The overlapping loci identified by the study may have implications for both bacterial function and human clinical disease.
Article
Microbiology
Sarah C. Bernard, M. Kay Washington, D. Borden Lacy
Summary: Infections caused by Paeniclostridium sordellii, a bacterium that produces toxins and spores anaerobically, are related to treatment-resistant toxic shock syndrome. A neutralizing monoclonal antibody against Clostridioides difficile toxin B (TcdB) has been found to potentially protect against P. sordellii infection. A mouse model was used to demonstrate the efficacy of the antibody and identify the impact of the mouse's reproductive cycle on disease symptoms.
Article
Microbiology
Kevin O. Childress, Caroline S. Cencer, Matthew J. Tyska, D. Borden Lacy
Summary: This study investigates the interactions between Clostridioides difficile and host cell receptors CSPG4 and Nectin-3. The localization of these receptors on colonic tissue and their role in disease promotion were explored using immunofluorescence microscopy. The findings suggest that Nectin-3 facilitates TcdB binding at the epithelial surface and shed soluble CSPG4-ECD derived from stromal cells contributes to TcdB intoxication of epithelial cells.
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.