Clostridium difficile in recent years has undergone rapid evolution and has emerged as a serious human pathogen. Proteomic approaches can improve the understanding of the diversity of this important pathogen, especially in comparing the adaptive ability of different C. difficile strains. In this study, TMT labeling and nanoLC-MS/MS driven proteomics were used to investigate the responses of four C. difficile strains to nutrient shift and osmotic shock. We detected 126 and 67 differentially expressed proteins in at least one strain under nutrition shift and osmotic shock, respectively. During nutrient shift, several components of the phosphotransferase system (PTS) were found to be differentially expressed, which indicated that the carbon catabolite repression (CCR) was relieved to allow the expression of enzymes and transporters responsible for the utilization of alternate carbon sources. Some classical osmotic shock associated proteins, such as GroEL, RecA, CspG, and CspF, and other stress proteins such as PurG and SerA were detected during osmotic shock. Furthermore, the recently emerged strains were found to contain a more robust gene network in response to both stress conditions. This work represents the first comparative proteomic analysis of historic and recently emerged hypervirulent C. difficile strains, complementing the previously published proteomics studies utilizing only one reference strain.
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http://dx.doi.org/10.1021/pr3007528 | DOI Listing |
Microorganisms
November 2024
Department of Clinical Microbiology, Infection Prevention and Control, University Hospital Centre Zagreb, Kispaticeva st. 12, 10000 Zagreb, Croatia.
We investigated the intra-hospital distribution of strains by whole-genome sequencing (WGS) of isolates collected in 2022 at the University Hospital Centre (UHC) Zagreb. In total, 103 patients with first-episode CDI in 2022 at UHC Zagreb were included, based on the screening stool antigen test for GDH (RidaQuick CD GDH; R-Biopharm AG, Germany), confirmed by Eazyplex assays (Eazyplex CD assay; AmplexDiagnostics GmbH, Germany) specific for A, B, and binary toxins. Demographic and clinical data were retrospectively analyzed from electronic medical records.
View Article and Find Full Text PDFNat Med
January 2025
Vedanta Biosciences, Inc., Cambridge, MA, USA.
Donor-derived fecal microbiota treatments are efficacious in preventing recurrent Clostridioides difficile infection (rCDI), but they have inherently variable quality attributes, are difficult to scale and harbor the risk of pathogen transfer. In contrast, VE303 is a defined consortium of eight purified, clonal bacterial strains developed for prevention of rCDI. In the phase 2 CONSORTIUM study, high-dose VE303 was well tolerated and reduced the odds of rCDI by more than 80% compared to placebo.
View Article and Find Full Text PDFGut Microbes
December 2025
Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
The development of fecal microbiota transplantation and defined live biotherapeutic products for the treatment of human disease has been an empirically driven process yielding a notable success of approved drugs for the treatment of recurrent infection. Assessing the potential of this therapeutic modality in other indications with mixed clinical results would benefit from consistent quantitative frameworks to characterize drug potency and composition and to assess the impact of dose and composition on the frequency and duration of strain engraftment. Monitoring these drug properties and engraftment outcomes would help identify minimally sufficient sets of microbial strains to treat disease and provide insights into the intersection between microbial function and host physiology.
View Article and Find Full Text PDFAppl Environ Microbiol
December 2024
Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA.
Sci Rep
December 2024
Foodborne and Waterborne Diseases Research Center , Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Clostridioides difficile is the leading cause of healthcare- and antibiotic-associated diarrhea. Surface layer protein A (SlpA), an essential component of the bacterium's outermost layer, contributes to colonization and inflammation. The peroxisome proliferator-activated receptor gamma (PPAR-γ) has been demonstrated to improve intestinal integrity and prevent inflammation in host cells.
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