Proteomic Signatures of <i>Clostridium difficile</i> Stressed with Metronidazole, Vancomycin, or Fidaxomicin
The anaerobic pathogen <i>Clostridium difficile</i> is of growing significance for the health care system due to its increasing incidence and mortality. As <i>C. difficile</i> infection is both supported and treated by antibiotics, a deeper knowledge on how antimicrobial agen...
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doaj-0035df66c00443a5a4678b9d3f8a409c2020-11-24T23:20:36ZengMDPI AGCells2073-44092018-11-0171121310.3390/cells7110213cells7110213Proteomic Signatures of <i>Clostridium difficile</i> Stressed with Metronidazole, Vancomycin, or FidaxomicinSandra Maaß0Andreas Otto1Dirk Albrecht2Katharina Riedel3Anke Trautwein-Schult4Dörte Becher5Institute of Microbiology, Department of Microbial Proteomics, University of Greifswald, Felix-Hausdorff-Str. 8, 17489 Greifswald, GermanyInstitute of Microbiology, Department of Microbial Proteomics, University of Greifswald, Felix-Hausdorff-Str. 8, 17489 Greifswald, GermanyInstitute of Microbiology, Department of Microbial Physiology and Molecular Biology, University of Greifswald, Felix-Hausdorff-Str. 8, 17489 Greifswald, GermanyInstitute of Microbiology, Department of Microbial Physiology and Molecular Biology, University of Greifswald, Felix-Hausdorff-Str. 8, 17489 Greifswald, GermanyInstitute of Microbiology, Department of Microbial Proteomics, University of Greifswald, Felix-Hausdorff-Str. 8, 17489 Greifswald, GermanyInstitute of Microbiology, Department of Microbial Proteomics, University of Greifswald, Felix-Hausdorff-Str. 8, 17489 Greifswald, GermanyThe anaerobic pathogen <i>Clostridium difficile</i> is of growing significance for the health care system due to its increasing incidence and mortality. As <i>C. difficile</i> infection is both supported and treated by antibiotics, a deeper knowledge on how antimicrobial agents affect the physiology of this important pathogen may help to understand and prevent the development and spreading of antibiotic resistant strains. As the proteomic response of a cell to stress aims at counteracting the harmful effects of this stress, it can be expected that the pattern of a pathogen’s responses to antibiotic treatment will be dependent on the antibiotic mechanism of action. Hence, every antibiotic treatment is expected to result in a specific proteomic signature characterizing its mode of action. In the study presented here, the proteomic response of <i>C. difficile</i> 630∆<i>erm</i> to vancomycin, metronidazole, and fidaxomicin stress was investigated on the level of protein abundance and protein synthesis based on 2D PAGE. The quantification of 425 proteins of <i>C. difficile</i> allowed the deduction of proteomic signatures specific for each drug treatment. Indeed, these proteomic signatures indicate very specific cellular responses to each antibiotic with only little overlap of the responses. Whereas signature proteins for vancomycin stress fulfil various cellular functions, the proteomic signature of metronidazole stress is characterized by alterations of proteins involved in protein biosynthesis and protein degradation as well as in DNA replication, recombination, and repair. In contrast, proteins differentially expressed after fidaxomicin treatment can be assigned to amino acid biosynthesis, transcription, cell motility, and the cell envelope functions. Notably, the data provided by this study hint also at so far unknown antibiotic detoxification mechanisms.https://www.mdpi.com/2073-4409/7/11/213<i>Clostridiodes difficile</i>antibioticsproteomicsprotein synthesis2D PAGE |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sandra Maaß Andreas Otto Dirk Albrecht Katharina Riedel Anke Trautwein-Schult Dörte Becher |
spellingShingle |
Sandra Maaß Andreas Otto Dirk Albrecht Katharina Riedel Anke Trautwein-Schult Dörte Becher Proteomic Signatures of <i>Clostridium difficile</i> Stressed with Metronidazole, Vancomycin, or Fidaxomicin Cells <i>Clostridiodes difficile</i> antibiotics proteomics protein synthesis 2D PAGE |
author_facet |
Sandra Maaß Andreas Otto Dirk Albrecht Katharina Riedel Anke Trautwein-Schult Dörte Becher |
author_sort |
Sandra Maaß |
title |
Proteomic Signatures of <i>Clostridium difficile</i> Stressed with Metronidazole, Vancomycin, or Fidaxomicin |
title_short |
Proteomic Signatures of <i>Clostridium difficile</i> Stressed with Metronidazole, Vancomycin, or Fidaxomicin |
title_full |
Proteomic Signatures of <i>Clostridium difficile</i> Stressed with Metronidazole, Vancomycin, or Fidaxomicin |
title_fullStr |
Proteomic Signatures of <i>Clostridium difficile</i> Stressed with Metronidazole, Vancomycin, or Fidaxomicin |
title_full_unstemmed |
Proteomic Signatures of <i>Clostridium difficile</i> Stressed with Metronidazole, Vancomycin, or Fidaxomicin |
title_sort |
proteomic signatures of <i>clostridium difficile</i> stressed with metronidazole, vancomycin, or fidaxomicin |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2018-11-01 |
description |
The anaerobic pathogen <i>Clostridium difficile</i> is of growing significance for the health care system due to its increasing incidence and mortality. As <i>C. difficile</i> infection is both supported and treated by antibiotics, a deeper knowledge on how antimicrobial agents affect the physiology of this important pathogen may help to understand and prevent the development and spreading of antibiotic resistant strains. As the proteomic response of a cell to stress aims at counteracting the harmful effects of this stress, it can be expected that the pattern of a pathogen’s responses to antibiotic treatment will be dependent on the antibiotic mechanism of action. Hence, every antibiotic treatment is expected to result in a specific proteomic signature characterizing its mode of action. In the study presented here, the proteomic response of <i>C. difficile</i> 630∆<i>erm</i> to vancomycin, metronidazole, and fidaxomicin stress was investigated on the level of protein abundance and protein synthesis based on 2D PAGE. The quantification of 425 proteins of <i>C. difficile</i> allowed the deduction of proteomic signatures specific for each drug treatment. Indeed, these proteomic signatures indicate very specific cellular responses to each antibiotic with only little overlap of the responses. Whereas signature proteins for vancomycin stress fulfil various cellular functions, the proteomic signature of metronidazole stress is characterized by alterations of proteins involved in protein biosynthesis and protein degradation as well as in DNA replication, recombination, and repair. In contrast, proteins differentially expressed after fidaxomicin treatment can be assigned to amino acid biosynthesis, transcription, cell motility, and the cell envelope functions. Notably, the data provided by this study hint also at so far unknown antibiotic detoxification mechanisms. |
topic |
<i>Clostridiodes difficile</i> antibiotics proteomics protein synthesis 2D PAGE |
url |
https://www.mdpi.com/2073-4409/7/11/213 |
work_keys_str_mv |
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