Review
Microbiology
Joshua Heuler, Louis-Charles Fortier, Xingmin Sun
Summary: Clostridioides difficile, formerly known as Clostridium difficile, is the causative agent of C. difficile infections, which pose challenges in healthcare settings. Antibiotic-induced dysbiosis allows C. difficile colonization in the gut. Phage infection offers potential new treatment strategies against C. difficile infections.
FEMS MICROBIOLOGY REVIEWS
(2021)
Review
Microbiology
Joshua Heuler, Louis-Charles Fortier, Xingmin Sun
Summary: Clostridioides difficile, previously known as Clostridium difficile, is the causative agent of CDI. Antibiotics-induced dysbiosis of the microbiota is the primary factor allowing C. difficile to colonize the gut and cause diseases. Phages infecting C. difficile could offer new treatment strategies and insights into its biology.
FEMS MICROBIOLOGY REVIEWS
(2021)
Review
Medicine, General & Internal
Andrew A. Umansky, Louis Charles Fortier
Summary: With the antibiotic crisis and the rise in antimicrobial resistance, new therapeutic alternatives are urgently needed. Phage therapy shows promise as an alternative, but there are challenges in treating pathogens like Clostridioides difficile. No strictly lytic phages have been identified for C. difficile, and its antiphage mechanisms and spore resistance complicate therapeutic interventions. However, recent advances in phage engineering and host recognition offer potential solutions for phage therapy in C. difficile.
FRONTIERS IN MEDICINE
(2023)
Review
Microbiology
Jennifer Venhorst, Jos M. B. M. van der Vossen, Valeria Agamennone
Summary: The pathogenic bacteria Clostridioides difficile and Clostridium perfringens pose a major threat to human and animal health. The increasing antibiotic resistance has led to the pursuit of novel strategies to combat these infections, including the use of bacteriophages. However, there are limitations to the use of bacteriophages that need to be considered and further research is necessary to optimize their potential.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Microbiology
Yannick D. N. Tremblay, Bruno Dupuy
Summary: This article discusses the relationship between metabolic reprogramming and biofilm formation in Clostridioides difficile, as well as its overlap with the sporulation cascade. The findings provide important clues for modeling biofilm formation. However, further research is needed to answer outstanding questions in the field.
CURRENT OPINION IN MICROBIOLOGY
(2022)
Review
Medicine, General & Internal
Eleftheria Kampouri, Antony Croxatto, Guy Prod'hom, Benoit Guery
Summary: Clostridioides difficile is a common pathogen with a wide clinical spectrum, and the debate over optimal diagnostic algorithms and treatment approaches continues. Progress has been made in treatment, but targeting the right population for expensive therapies remains a major challenge.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Xinyun Cao, Hande Boyaci, James Chen, Yu Bao, Robert Landick, Elizabeth A. Campbell
Summary: Fidaxomicin is effective in treating Cdiff infections with minimal impact on gut commensals, and its activity is determined by a specific binding determinant in Cdiff RNA polymerase.
Article
Microbiology
Alexia L. M. Royer, Andrew A. Umansky, Marie-Maude Allen, Julian R. Garneau, Maicol Ospina-Bedoya, Joseph A. Kirk, Gregory Govoni, Robert P. Fagan, Olga Soutourina, Louis-Charles Fortier
Summary: Therapeutic bacteriophages are being considered as alternatives to treat Clostridioides difficile infections. The surface layer protein A (SlpA) is identified as a common receptor used by many phages, which is a significant discovery for the rational design of therapeutic phage cocktails.
MICROBIOLOGY SPECTRUM
(2023)
Review
Virology
Janet Y. Nale, Anisha M. Thanki, Srwa J. Rashid, Jinyu Shan, Gurinder K. Vinner, Ahmed S. A. Dowah, Jeffrey K. J. Cheng, Thomas Sicheritz-Ponten, Martha R. J. Clokie
Summary: Current conventional treatment for Clostridioides difficile infection (CDI) relies on antibiotics, but the emergence of antibiotic-resistant strains has led to persistent high CDI cases and recurrent infections. Bacteriophages are being investigated as alternative therapeutics for their precision in killing bacteria.
Review
Immunology
Hamideh Raeisi, Masoumeh Azimirad, Ali Nabavi-Rad, Hamid Asadzadeh Aghdaei, Abbas Yadegar, Mohammad Reza Zali
Summary: Clostridioides difficile is a major cause of antibiotic-associated diarrhea and one of the most common healthcare-associated bacterial infections worldwide. Antibody therapy, particularly the use of recombinant antibodies generated through in vitro technologies, has shown promise in treating CDI. These approaches have the potential to overcome the limitations of the immune system and improve the sensitivity and specificity of the antibodies.
FRONTIERS IN IMMUNOLOGY
(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.
Article
Microbiology
M. J. Whittle, T. W. Bilverstone, R. J. van Esveld, A. C. Luecke, M. M. Lister, S. A. Kuehne, N. P. Minton
Summary: Bacteriophages show promise as an alternative treatment for Clostridioides difficile infection. Researchers isolated four novel C. difficile myoviruses, including Phi CD1801, which demonstrated broad host range activity against relevant strains. The study also identified SIpA as a potential phage receptor, highlighting the need for further research on phages with activity against specific bacterial strains. These findings provide important insights for the development of effective phage therapy for C. difficile infection.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biochemistry & Molecular Biology
Manuela Fuchs, Vanessa Lamm-Schmidt, Tina Lence, Johannes Sulzer, Arne Bublitz, Janet Wackenreuter, Milan Gerovac, Till Strowig, Franziska Faber
Summary: The anaerobic pathogen Clostridioides difficile forms antibiotic-resistant endospores to persist in the intestinal tract and cause recurrent infections. Through RIL-seq, we identified a network of small RNAs that bind to sporulation-related genes, and discovered that SpoX and SpoY regulate the translation of the master regulator of sporulation, Spo0A, in an opposing manner, leading to altered sporulation rates. Deletion mutants of SpoX and SpoY showed global effects on gut colonization and intestinal sporulation in antibiotic-treated mice. Our study uncovers a complex RNA-RNA interactome controlling the physiology and virulence of C. difficile and identifies a complex post-transcriptional layer in the regulation of spore formation in this important human pathogen.
Review
Microbiology
Hamideh Raeisi, Masoumeh Azimirad, Hamid Asadzadeh Aghdaei, Abbas Yadegar, Mohammad Reza Zali
Summary: Clostridioides difficile (C. difficile) is a common cause of nosocomial diarrhea and the emergence of hypervirulent strains has led to efforts in developing accurate diagnostic methods. Antibody-based ultrasensitive diagnostic platforms, particularly those using recombinant antibodies (rAbs), have shown promising results in both research and clinical settings. These platforms offer high sensitivity and specificity, and the use of rAb technologies allows for faster and more cost-effective antibody production.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Microbiology
Heloise Coullon, Thomas Candela
Summary: The cortex and peptidoglycan of Clostridioides difficile have been relatively understudied, but have gained increased interest in recent years due to their highly modified structures. These modifications may play a role in antimicrobial resistance and are crucial for spore cortex synthesis and germination, which are essential in the pathogenesis of the bacterium. Enzymes responsible for these modifications could be potential new drug targets or anti-C. difficile agents.
CURRENT OPINION IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anna Maikova, Johann Peltier, Pierre Boudry, Eliane Hajnsdorf, Nicolas Kint, Marc Monot, Isabelle Poquet, Isabelle Martin-Verstraete, Bruno Dupuy, Olga Soutourina
NUCLEIC ACIDS RESEARCH
(2018)
Review
Food Science & Technology
Olga Soutourina
Article
Biotechnology & Applied Microbiology
Anna Maikova, Victor Kreis, Anais Boutserin, Konstantin Severinov, Olga Soutourina
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2019)
Review
Genetics & Heredity
Emma Piattelli, Johann Peltier, Olga Soutourina
Article
Biology
Johann Peltier, Audrey Hamiot, Julian R. Garneau, Pierre Boudry, Anna Maikova, Eliane Hajnsdorf, Louis-Charles Fortier, Bruno Dupuy, Olga Soutourina
COMMUNICATIONS BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Pierre Boudry, Emma Piattelli, Emilie Drouineau, Johann Peltier, Anais Boutserin, Maxence Lejars, Eliane Hajnsdorf, Marc Monot, Bruno Dupuy, Isabelle Martin-Verstraete, Daniel Gautheret, Claire Toffano-Nioche, Olga Soutourina
Summary: High-throughput sequencing of RNA immunoprecipitation revealed a diverse set of mRNAs and ncRNAs interacting with the RNA chaperone protein Hfq in C. difficile, shedding light on the post-transcriptional regulatory network of this pathogen.
Article
Microbiology
Anna Maikova, Pierre Boudry, Anna Shiriaeva, Aleksandra Vasileva, Anais Boutserin, Sofia Medvedeva, Ekaterina Semenova, Konstantin Severinov, Olga Soutourina
Summary: CRISPR-Cas systems provide prokaryotes with adaptive immunity against foreign nucleic acid invaders. This study demonstrates the adaptation process of the type I-B CRISPR-Cas system in Clostridioides difficile and its functional link between adaptation and interference machineries. Understanding the functional PAM motifs and activity levels of CRISPR arrays in this pathogen is crucial for future biotechnological and medical applications.
Article
Biochemistry & Molecular Biology
Marine Oberkampf, Audrey Hamiot, Pamela Altamirano-Silva, Paula Belles-Sancho, Yannick D. N. Tremblay, Nicholas DiBenedetto, Roland Seifert, Olga Soutourina, Lynn Bry, Bruno Dupuy, Johann Peltier
Summary: The production and degradation of cyclic diadenosine monophosphate (c-di-AMP) play important roles in the growth, environmental adaptation, and infection of the human enteropathogen Clostridioides difficile. The production of c-di-AMP is essential for growth, potassium uptake, biofilm formation, and cell wall homeostasis, while its degradation is required for osmotolerance and resistance to detergents and bile salts. Additionally, c-di-AMP degradation is important for host colonization.
Article
Microbiology
Alexia L. M. Royer, Andrew A. Umansky, Marie-Maude Allen, Julian R. Garneau, Maicol Ospina-Bedoya, Joseph A. Kirk, Gregory Govoni, Robert P. Fagan, Olga Soutourina, Louis-Charles Fortier
Summary: Therapeutic bacteriophages are being considered as alternatives to treat Clostridioides difficile infections. The surface layer protein A (SlpA) is identified as a common receptor used by many phages, which is a significant discovery for the rational design of therapeutic phage cocktails.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Polina Muzyukina, Anton Shkaruta, Noemi M. Guzman, Jessica Andreani, Adair L. Borges, Joseph Bondy-Denomy, Anna Maikova, Ekaterina Semenova, Konstantin Severinov, Olga Soutourina
Summary: CRISPR-Cas systems provide prokaryotic hosts with adaptive immunity against mobile genetic elements. Many bacteriophages encode anti-CRISPR (Acr) proteins that inhibit host defense. This study reports the discovery of a novel Acr protein, AcrIB2, which efficiently inhibits interference by the host's CRISPR-Cas system.
Article
Microbiology
Isabelle Poquet, Laure Saujet, Alexis Canette, Marc Monot, Jovanna Mihajlovic, Jean-Marc Ghigo, Olga Soutourina, Romain Briandet, Isabelle Martin-Verstraete, Bruno Dupuy
FRONTIERS IN MICROBIOLOGY
(2018)
Article
Biotechnology & Applied Microbiology
Julian R. Garneau, Ognjen Sekulovic, Bruno Dupuy, Olga Soutourina, Marc Monot, Louis-Charles Fortier
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2018)