PXD039809-1

PXD039809 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis of metronidazole resistance in the human facultative pathogen Bacteroides fragilis
Description	Bacteroides 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.
HostingRepository	PRIDE
AnnounceDate	2023-03-20
AnnouncementXML	Submission_2023-03-20_07:14:56.750.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AnaPaunkov
SpeciesList	scientific name: Bacteroides fragilis (strain 638R); NCBI TaxID: 862962;
ModificationList	iodoacetamide derivatized residue
Instrument	orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-02 08:33:11	ID requested
⏵ 1	2023-03-20 07:14:57	announced

Dataset with its publication pending

submitter keyword: shotgun proteomics,Bacteroides fragilis, metronidayole resistance

DavidLeitsch
contact affiliation	Medical University of Vienna
contact email	david.leitsch@meduniwien.ac.at
lab head
AnaPaunkov
contact affiliation	Medical University of Vienna
contact email	ana.paunkov@meduniwien.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039809
     1. Label: PRIDE project
     2. Name: Proteomic analysis of metronidazole resistance in the human facultative pathogen Bacteroides fragilis