Characterization of Clostridioides difficile DSM 101085 with A-B-CDT+ Phenotype from a Late Recurrent Colonization.

Thomas Riedel, Meina Neumann-Schaal, Johannes Wittmann, Isabel Schober, Julia Danielle Hofmann, Chia-Wen Lu, Antonia Dannheim, Ortrud Zimmermann, Matthias Lochner, Uwe Groß, Jörg Overmann

Journal: Genome biology and evolution 2021;12(5):566-577

PMID: 32302381

Abstract

During the last decades, hypervirulent strains of Clostridioides difficile with frequent disease recurrence and increased mortality appeared. Clostridioides difficile DSM 101085 was isolated from a patient who suffered from several recurrent infections and colonizations, likely contributing to a fatal outcome. Analysis of the toxin repertoire revealed the presence of a complete binary toxin locus and an atypical pathogenicity locus consisting of only a tcdA pseudogene and a disrupted tcdC gene sequence. The pathogenicity locus shows upstream a transposon and has been subject to homologous recombination or lateral gene transfer events. Matching the results of the genome analysis, neither TcdA nor TcdB production but the expression of cdtA and cdtB was detected. This highlights a potential role of the binary toxin C. difficile toxin in this recurrent colonization and possibly further in a host-dependent virulence. Compared with the C. difficile metabolic model strains DSM 28645 (630Δerm) and DSM 27147 (R20291), strain DSM 101085 showed a specific metabolic profile, featuring changes in the threonine degradation pathways and alterations in the central carbon metabolism. Moreover, products originating from Stickland pathways processing leucine, aromatic amino acids, and methionine were more abundant in strain DSM 101085, indicating a more efficient use of these substrates. The particular characteristics of strain C. difficile DSM 101085 may represent an adaptation to a low-protein diet in a patient with recurrent infections.

© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Address: Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany.; Department of Bioinformatics and Biochemistry and Braunschweig Integrated Centre of Systems Biology (BRICS), Technische Universität Braunschweig, Germany.; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.; Institute of Medical Microbiology, University Medical Center Göttingen, Germany.; Göttingen International Health Network, Göttingen, Germany.; Institute of Microbiology, Technical University of Braunschweig, Germany.
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