Plasmid Acquisition Alters Vancomycin Susceptibility in Clostridioides difficile
| Autor: | Gary M. Dunny, Gaurav K. Behera, Scott A. Cunningham, Robin Patel, Meng Pu, Jun Chen, Sarah Becker, Janice M. Cho, Purna C. Kashyap, Patricio Jeraldo, Yava Jones-Hall, Kerryl E. Greenwood-Quaintance, Talal Amjad, Helena Mendes-Soares |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Severe disease Microbial Sensitivity Tests Article Microbiology Mice 03 medical and health sciences 0302 clinical medicine Plasmid Antibiotic resistance Vancomycin Drug Resistance Bacterial medicine Animals Germ-Free Life Humans In patient Gastrointestinal tract Whole Genome Sequencing Hepatology Clostridioides difficile business.industry Gastroenterology Anti-Bacterial Agents Disease Models Animal 030104 developmental biology Humanized mouse Clostridium Infections 030211 gastroenterology & hepatology business Clostridioides Plasmids medicine.drug |
| Zdroj: | Gastroenterology |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/j.gastro.2020.10.046 |
| Popis: | The increasing incidence of primary and recurring Clostridioides difficile infections (CDI), which evade current treatment strategies, reflects the changing biology of C difficile. Here, we describe a putative plasmid-mediated mechanism potentially driving decreased sensitivity of C difficile to vancomycin treatment. We identified a broad host range transferable plasmid in a C difficile strain associated with lack of adequate response to vancomycin treatment. The transfer of this plasmid to a vancomycin-susceptible C difficile isolate decreased its susceptibility to vancomycin in vitro and resulted in more severe disease in a humanized mouse model. Our findings suggest plasmid acquisition in the gastrointestinal tract to be a possible mechanism underlying vancomycin treatment failure in patients with CDI, but further work is needed to characterize the mechanism by which plasmid genes determine vancomycin susceptibility in C difficile. |
| Databáze: | OpenAIRE |
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