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PXD039809-1

PXD039809 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomic analysis of metronidazole resistance in the human facultative pathogen Bacteroides fragilis
DescriptionBacteroides fragilis is an anaerobic commensal in the human gut which can act as opportunistic pathogen when leaving its intestinal niche to reach other body sites. Bacteroides infections have a high lethality and must be treated by antimicrobial chemotherapy. Metronidazole is one of the most frequently administered antimicrobials in the treatment of Bacteroides infections and is highly reliable. However, metronidazole resistance does occur, favoring fatal disease outcomes. Most of the resistant isolates harbor a nim gene (12 are currently known, i.e. nimA to nimL), a transferable resistance determinant for metronidazole. Previous research suggested that Nim proteins might affect the cellular physiology by changing the activity of key enzymes like pyruvate:ferredoxin oxidoreductase (PFOR). In this study we wanted to assess the impact of the nimA gene on protein expression in a standard B. fragilis isolate, 638R, and compared overall protein expression in 638R with and without a nim gene and with the nimA gene in a proteomic study. Further, high-level metronidazole resistance was induced in both strains and the protein expression profiles of resulting resistant daughter strains were also compared with their respective parent strains. We found that comparably few proteins displayed altered expression in 638R with the nimA gene, but flavodiiron protein FprA was repeatedly found upregulated. FprA is often found in anaerobes and reduces molecular oxygen to water and/or nitric oxide to nitrous oxide. After induction of metronidazole resistance, a far higher number of proteins were found to be differentially expressed in 638R without nimA than in 638R with nimA. In the former, factors for the import of hemin were strongly downregulated, indicating impaired iron import, whereas in the latter the observed changes were not only less numerous but also less specific. Based on the results of this study we present a novel hypothetic model of metronidazole resistance and Nim function.
HostingRepositoryPRIDE
AnnounceDate2023-03-20
AnnouncementXMLSubmission_2023-03-20_07:14:56.750.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAnaPaunkov
SpeciesList scientific name: Bacteroides fragilis (strain 638R); NCBI TaxID: 862962;
ModificationListiodoacetamide derivatized residue
Instrumentorbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-02-02 08:33:11ID requested
12023-03-20 07:14:57announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: shotgun proteomics,Bacteroides fragilis, metronidayole resistance
Contact List
DavidLeitsch
contact affiliationMedical University of Vienna
contact emaildavid.leitsch@meduniwien.ac.at
lab head
AnaPaunkov
contact affiliationMedical University of Vienna
contact emailana.paunkov@meduniwien.ac.at
dataset submitter
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Dataset FTP location
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