Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1013962 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project 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.
2023-03-20 | PXD039809 | Pride
Project description:Trichomonas vaginalis is a sexually transmitted human parasite causing trichomoniasis, leading to vaginitis or cervicitis in many patients. Furthermore, infections can lead to premature labour or loss of child as well as an increase in the risk of contracting HIV. For treatment the antibiotic 5-nitroimidazole metronidazole is commonly used, however antibiotic resistance in TV is on the rise, and the mechanism of how the parasite becomes resistant is not yet known. The aim of the study thus was to unravel the mechanism of resistance formation, by understanding the change in protein expression of the parasite. For this we studied different clinical isolates (i.e. various strains of TV) that were either sensitive or resistant to metronidazole, or resistance has been induced in a lab strain. It was previously known, that when sensitive TV cells are depleted of iron, they appear to have the same characteristics as resistant cell lines, however remained sensitive to the drug. Several proteins were identified, where the protein expression differed between the same cell line where either cells were depleted of iron, or resistance was induced. These proteins (mainly reductive agents) were studied on more detail. To understand the mechanism of metronidazole resistance.
2025-03-10 | PXD051345 | Pride
Project description:In vitro studies have described metronidazole (MTZ) resistance and the potential mechanisms involved. Costs to fitness and adaptive responses associated with resistance, however, have not been investigated. In this study we generated an HM-1-derived strain resistant to 12 µM MTZ (MTZR). We examined its phenotypic and transcriptional profile to determine the consequences and mRNA level changes associated with MTZ resistance. The expression profile of 9,230 genes in wild-type and metronidazole-resistant strains was compared. Transcriptome analysis revealed 142 differentially expressed genes in MTZR. In contrast to other MTZ-resistant parasites, MTZR did not down-regulate pyruvate:ferredoxin oxidoreductase, but showed increased expression of genes for a hypothetical protein (HP1) and several iron-sulfur flavoproteins, and the downregulation of genes for leucin-rich proteins. Overexpression of HP1-HA did not confer MTZR level of resistance, but provided a slight advantage in cell survival. Fisher's exact test showed 24 significantly enriched GO terms in MTZR, and a 3-way comparison of modulated genes with MTZR cultured without MTZ and HM-1 cultured with MTZ showed that 88 genes were specific to MTZR.
2012-02-22 | GSE35990 | GEO
Project description:In vitro studies have described metronidazole (MTZ) resistance and the potential mechanisms involved. Costs to fitness and adaptive responses associated with resistance, however, have not been investigated. In this study we generated an HM-1-derived strain resistant to 12 µM MTZ (MTZR). We examined its phenotypic and transcriptional profile to determine the consequences and mRNA level changes associated with MTZ resistance. The expression profile of 9,230 genes in wild-type and metronidazole-resistant strains was compared. Transcriptome analysis revealed 142 differentially expressed genes in MTZR. In contrast to other MTZ-resistant parasites, MTZR did not down-regulate pyruvate:ferredoxin oxidoreductase, but showed increased expression of genes for a hypothetical protein (HP1) and several iron-sulfur flavoproteins, and the downregulation of genes for leucin-rich proteins. Overexpression of HP1-HA did not confer MTZR level of resistance, but provided a slight advantage in cell survival. Fisher's exact test showed 24 significantly enriched GO terms in MTZR, and a 3-way comparison of modulated genes with MTZR cultured without MTZ and HM-1 cultured with MTZ showed that 88 genes were specific to MTZR. Wild-type and the MTZ-resistant strain MTZR were cultured either in the presence or absence of MTZ. 2 biological replicates per strain/condition.
2012-02-22 | E-GEOD-35990 | biostudies-arrayexpress
Project description:We aimed to delineate mechanisms of T. vaginalis resistance using transcriptome profiling of metronidazole (MTZ)-resistant and sensitive T. vaginalis clinical isolates.
2023-04-30 | GSE227448 | GEO
Project description:Previously, we have shown that in Entamoeba histolytica, methionine γ-lyase (EhMGL) downregulation results in trifluoromethionine resistance. The transcriptional response, however, of this parasite to the drug is not known. In this study, we used microarray analysis to determine if additional genes are involved. The expression profile of 9,230 genes in wild type and trifluoromethionine resistant strains was compared. Episomal overexpression of EhBspA1 was performed to verify its role in trifluoromethionine resistance. The transcriptomes of trifluoromethionine resistant strain cultured with or without trifluoromethionine, EhMGL-gene silenced strain, metronidazole resistant strain, and wild type strain under cysteine-deprived conditions were compared to determine the specificity of the changes observed in trifluoromethionine resistant strain.
2011-11-16 | E-GEOD-32314 | biostudies-arrayexpress
Project description:Giardia intestinalis metronidazole resistance series
| PRJNA323518 | ENA
Project description:The mechanism of 3-HP tolerance related to YieP was elucidated. The genome-wide analysises were carried out to find out the genes reponsible for 3-HP tolerance.
2022-07-02 | GSE133708 | GEO
Project description:Bacterial vaginosis (BV) treatment failures or recurrences are common. To identify features associated with treatment response, we compared vaginal microbiota and host ectocervical transcriptome before and after oral metronidazole therapy. Response to metronidazole is characterized by significant changes in chemokines and related transcripts suggesting that strategies to promote these pathways may prove beneficial.
2021-05-21 | GSE174799 | GEO