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ABSTRACT:
PROVIDER: PRJEB47276 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Regulatory RNAs (sRNAs) are now considered as major players in many physiological and adaptive responses in pathogenic bacteria. sRNAs have been extensively studied in Gram-negative bacteria, but less information is available in Gram-positive pathogens. There is a spread of multidrug-resistant (MDR) opportunistic organisms, grouped as “ESKAPE” pathogens, which comprise enterococci, a leading cause of hospital-acquired infections and outbreaks with emergence of MDR isolates, especially vancomycin-resistant Enterococcus faecium (VREF). Note that no information about sRNA expression is known in this major opportunistic pathogen. By transcriptomic and genomic analyses using E. faecium Aus0004 reference strain, 249 transcribed IGRs, including sRNA candidates, were detected and, using a series of cut-offs, this set was lowered down to 54 sRNAs while 7 that were predicted based on comparative sequence analysis. RNA-seq was performed with and without subinhibitory concentrations (SIC) of daptomycin, a cyclic lipopeptide antibiotic used for VREF infections. Under daptomycin SIC exposure, 260 genes (9.1% of the genome) had a significant alteration of expression including 80 upregulated genes and 180 downregulated genes. Among the repressed genes, a large proportion (55%) coded for proteins involved in carbohydrate and transport metabolism. Also, we focused on the 9 sRNAs exhibiting the highest expression, and all of them were confirmed as expressed along bacterial growth by Northern blots and qPCR. Out of these 9 sRNAs, four had significantly lower or higher expression in the presence of daptomycin SIC, and therefore responded to antibiotic exposure. Finally, we also tested the expression of these 9 sRNAs in a collection of isogenic Aus0004 mutants with increasing levels of daptomycin resistance, and we observed by qPCR that some sRNAs had a significantly modified expression in daptomycin resistance mutants. It highlights the significant implication of some of the E. faecium sRNAs in the early steps of the development of daptomycin resistance. This is the first experimental genome-wide sRNA identification in Gram-positive E. faecium, a leading cause of hospital acquired infections.
2017-02-16 | GSE94924 | GEO
Project description:This study aims to determine the global gene expression in vancomycin resistant Enterococcus faecium (VRE) in response to a novel essential oil-vancomycin combination, and the individual components (vancomycin, carvacrol and cuminaldehyde) to help determine the mechanism of action of this antimicrobial formulation. This formulation increases the susceptibility of VRE to vancomycin and the array provides data on the synergistic mechanism of action. Five conditions (1. Control; 2. Carvacrol, 1.98 mM; 3. Cuminaldehyde, 4.20 mM; 4. Vancomycin, 0.031 mg/l; 5. Combination, 1.98 mM Carvacrol, 4.2 mM Cuminaldehyde, 0.031 mg/l vancomycin) all with 1% DMSO were tested in triplicate with a 60 minute exposure time before extraction.
2019-12-31 | E-MTAB-8072 | biostudies-arrayexpress
Project description:Daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant Enterococcus faecium
| PRJNA673360 | ENA
Project description:The rise of antibiotic resistance and decline of antibiotic discovery urgently calls for novel mechanistic understanding of pharmacological and evolutionary interactions between antibiotics and multidrug resistant bacteria to revitalize existing antibiotics. The evolutionary cross-resistance to antibiotics has received intensive attention previously. Nevertheless, whether and how bacteria develop negative responses, under the selective pressure of antibiotics by inverting the evolutionary trajectory remains unclear. Here we found an instance of collateral sensitivity, in which clinical vancomycin-resistant Enterococcus faecium (VREfm) pathogens exhibit dramatic and specific susceptibility to pleuromutilin antibiotics, decreased minimal inhibitory concentrations (MICs) from 128 µg/mL to 0.03 µg/mL. The unique trade-off between vancomycin and pleuromutilins is mediated by the epistasis between the van gene cluster and msrC encoding an ABC-F protein protecting bacterial ribosomes. We validated the efficacy of pleuromutilins in vivo through reducing colonization and promoting microbiota restoration. Our findings provide an alternative approach to inverting the selective advantage and reversing the route of vancomycin resistance evolution, and to treat VREfm associated infections.
2022-05-20 | PXD030906 | Pride
Project description:Staphylococcus aureus is a notorious bacterial pathogen that causes a broad range of human diseases, and isolates that are resistant to several antibiotic classes including last resort antibiotics like vancomycin and daptomycin complicate the situation. We characterized S. aureus VC40, a strain that shows full resistance to vancomycin (MIC of 64 M-BM-5g/ml) and daptomycin (MIC of 4 M-BM-5g/ml) as well as a decreased susceptibility to further cell wall active agents. Genome sequencing revealed mutations in genes encoding the histidine kinases WalK and VraS that control cell envelope related processes and gene expression profiling indicated the induction of the respective regulons in strain VC40. Reconstitution of the mutations in walK or vraS into the susceptible S. aureus NCTC 8325 background resulted in a considerably increased resistance to vancomycin and daptomycin with MICs surpassing the clinical breakpoints for these antibiotics, thereby generating vancomycin-intermediate S. aureus (VISA) strains. As observed for S. aureus VC40, the walKwalk and vraS mutations also led to an increased expression of the respective regulons in the NCTC 8325 background. Phenotypic studies showed that S. aureus VC40 as well as the walKwalk and vraS mutants of strain NCTC 8325 were characterized by a significantly thickened cell wall, a decreased growth rate, a reduced autolytic activity and an increased resistance to lysostaphin-induced lysis. These results demonstrate that the WalK and VraS histidine kinases act as major switches which allow S. aureus to rapidly develop vancomycin resistance up to the VISA level via mutation of one single gene locus and concomitantly contribute to cross-resistance to other antibiotics including the last resort antibiotic daptomycin. Microarray was used to evaluate alteration in the transcriptome of mutS mutant and compared to the parental strain VC40
2014-08-18 | E-GEOD-46887 | biostudies-arrayexpress
Project description:Preliminary analysis on extracts (pellets and supernatant) of vancomycin-resistant Enterococcus faecium strains cultured in BHI media. Untargeted LC-MS/MS acquisition performed in positive ion mode.
| MSV000092864 | GNPS
Project description:Daptomycin (DAP) is the last-resort treatment for heterogeneous Vancomycin-Intermediate-Staphylococcus aureus (hVISA) and Vancomycin-Intermediate-S.aureus (VISA), and DAP-resistance onset which is also linked to reduced vancomycin susceptibility, is an increasing public health problem. To have more insight into the mechanisms of daptomycin resistance, the comparative transcriptomes of two DAP-R (1C-3B) clinical isogenic isolates vs their DAP-S (1A-3A) counterparts were investigated by Illumina RNA-seq, the Rockhopper tool, computational filtering analyses and bioinformatic tools.
2020-08-07 | GSE121797 | GEO
Project description:Linezolid - vancomycin resistant enterococcus faecium
| PRJNA607166 | ENA
Project description:Staphylococcus aureus is a notorious bacterial pathogen that causes a broad range of human diseases, and isolates that are resistant to several antibiotic classes including last resort antibiotics like vancomycin and daptomycin complicate the situation. We characterized S. aureus VC40, a strain that shows full resistance to vancomycin (MIC of 64 µg/ml) and daptomycin (MIC of 4 µg/ml) as well as a decreased susceptibility to further cell wall active agents. Genome sequencing revealed mutations in genes encoding the histidine kinases WalK and VraS that control cell envelope related processes and gene expression profiling indicated the induction of the respective regulons in strain VC40. Reconstitution of the mutations in walK or vraS into the susceptible S. aureus NCTC 8325 background resulted in a considerably increased resistance to vancomycin and daptomycin with MICs surpassing the clinical breakpoints for these antibiotics, thereby generating vancomycin-intermediate S. aureus (VISA) strains. As observed for S. aureus VC40, the walKwalk and vraS mutations also led to an increased expression of the respective regulons in the NCTC 8325 background. Phenotypic studies showed that S. aureus VC40 as well as the walKwalk and vraS mutants of strain NCTC 8325 were characterized by a significantly thickened cell wall, a decreased growth rate, a reduced autolytic activity and an increased resistance to lysostaphin-induced lysis. These results demonstrate that the WalK and VraS histidine kinases act as major switches which allow S. aureus to rapidly develop vancomycin resistance up to the VISA level via mutation of one single gene locus and concomitantly contribute to cross-resistance to other antibiotics including the last resort antibiotic daptomycin.
2014-08-18 | GSE46887 | GEO