Ontology highlight
ABSTRACT:
PROVIDER: PRJNA764862 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15992902_1.fastq.gz | Fastqsanger.gz | |||
| SRR15992902_2.fastq.gz | Fastqsanger.gz | |||
| SRR15992903_1.fastq.gz | Fastqsanger.gz | |||
| SRR15992903_2.fastq.gz | Fastqsanger.gz | |||
| SRR15992904_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 10 |
Similar Datasets
Project description:Antibiotic resistance continues to rise as a global health threat. Novel anti-virulence strategies diminish the drive for evolutionary pressure, but still hinder a pathogen’s ability to infect a host. Treatment of the highly virulent Pseudomonas aeruginosa strain PA14 with virulence inhibitors (R-2 and R-6) elicited widely varying transcriptional profiles. Of interest, expression of a family of resistance-nodulation-division (RND) efflux pumps implicated in the intrinsic drug resistance of P. aeruginosa, was significantly altered by R-2 and R-6 treatment. While structurally similar, these inhibitors caused differential expression of various RND efflux pumps within the Mex family—R-2 treatment stimulated expression of mexEF-oprN while R-6 treatment led to increased mexAB-oprM expression. Further expansion into a small library of virulence inhibitors revealed chemical motifs that trigger increases in RND efflux pump expression. Additionally, activation of these efflux pumps suggests low accumulation of virulence inhibitors in WT PA14. Treatment of an efflux pump-deficient strain with R-2 or R-6 resulted in inhibition of several virulence factors, for example R-2 was found to abolish swimming motility. Collectively, treatment with either R-2 or R-6 gives rise to a convoluted transcriptomic response, confounded by the impact of efflux pump expression on the system. However, understanding the moieties that lead to high expression of the efflux pumps enables further rational design of novel virulence inhibitors that do not cause RND efflux pump activation.
2025-08-13 | GSE291940 | GEO
Project description:Repurposing bioactive aporphine alkaloids as efflux pump inhibitors
| PRJNA416141 | ENA
Project description:Efflux pumps are a significant challenge for the development of new antibacterial agents. Overcoming efflux requires an in-depth understanding of efflux pump functions, substrate specificities, and the development of inhibitors. However, the complexities of drug efflux networks have limited such studies. To address these challenges, we report the generation of Efflux KnockOut-35 (EKO-35), a highly susceptible Escherichia coli strain lacking 35 efflux pumps. We demonstrate the utility of this strain by constructing an efflux platform consisting of strains individually expressing genes encoding efflux pumps forming tripartite complexes with the outer membrane channel TolC. This platform was profiled against a curated diverse compound collection, which enabled us to define physicochemical properties that contribute to transport. We also show the E. coli drug efflux network is conditionally essential for growth, and that the platform can be used to investigate efflux pump inhibitor specificities and also efflux pump interplay. We believe EKO-35 and the efflux platform will have widespread application for the study of drug efflux.
2022-08-31 | PXD033975 | Pride
Project description:Target (MexB) and efflux based mechanisms decreasing the effectiveness of the efflux pump inhibitor D13-9001 in P. aeruginosa PAO1: uncovering a new role for MexMN-OprM in efflux of β-lactams and a novel regulatory circuit (MmnRS) controlling MexMN expression Efflux pumps contribute to antibiotic resistance in Gram-negative pathogens. Correspondingly, efflux pump inhibitors (EPIs) may reverse this resistance. D13-9001 specifically inhibits MexAB-OprM in P. aeruginosa. Mutants with decreased susceptibility to MexAB-OprM inhibition by D13-9001 were identified and these fell into two categories; those having alterations in the target MexB (F628L and ΔV177) and those with mutations in PA1438 (L172P substitution) which encoded a putative sensor kinase of unknown function. The alterations in MexB were consistent with reported structural studies of D13-9001 interaction with MexB. The PA1438L172P alteration mediated a >150-fold upregulation of MexMN pump gene expression and >50-fold upregulation of PA1438 and the neighboring response regulator gene PA1437. We propose that these be renamed as mmnR/mmnS for MexMN Regulator and Sensor. MexMN was shown to partner with the outer membrane channel protein OprM and to pump several β-lactams, monobactams and tazobactam. Upregulated MexMN functionally replaced MexAB-OprM to efflux these compounds but was insusceptible to inhibition by D13-9001. MmnSL172P also mediated a decrease in susceptibility to imipenem / biapenem that was independent of MexMN-OprM. Expression of oprD, encoding the uptake channel for these compounds was downregulated, suggesting that this channel is also part of the MmnSR regulon. RNA-seq of cells encoding MmnSL172P revealed among other things an interrelationships between regulation of mexMN and genes involved in heavy metal resistance.
2018-12-07 | GSE123403 | GEO
Project description:Efflux pumps of the resistance-nodulation-division (RND) superfamily, particularly the AcrAB-TolC and MexAB-OprM, besides mediating intrinsic and acquired resistance, also intervene in bacterial pathogenicity. Inhibitors of such pumps could restore activities of antibiotics and curb bacterial virulence. Here, we identify pyrrole-based compounds that boost antibiotic activity in Escherichia coli and Pseudomonas aeruginosa by inhibiting their archetype RND transporters. The discovered efflux pump inhibitors (EPIs) inhibit the efflux of fluorescent probes, attenuate persister formation, and diminish resistant mutant development. Molecular docking and biophysical studies revealed that the EPIs bind to AcrB. EPIs also possess an anti-pathogenic potential and attenuate P. aeruginosa virulence in vivo. The excellent efficacy of the EPI-antibiotic combination was evidenced in animal lung infection and sepsis protection models. These findings indicate that EPIs discovered herein with no off-target effects and negligible toxicity are potential antibiotic adjuvants to address life-threatening bacterial infections.
2024-03-18 | GSE210309 | GEO
Project description:In this study, we investigated the role of efflux pump genes in linezolid resistance. M. tuberculosis H37Rv cultures were exposed to sub-inhibitory concentrations of linezolid (¼ MIC) for 24 hours, and transcriptomic analysis was performed to identify upregulated genes. Of the 120 genes involved in cell wall processes, 9/120 (7.5%) were efflux pump genes, primarily belonging to the ATP-binding cassette (ABC), major facilitator superfamily (MFS), resistance nodulation division (RND), and small multidrug resistance (SMR) families. qRT-PCR, performed at 1/2, 1/4 and 1/8 MIC of linezolid, confirmed the RNA-seq results, showing that 8/9 (88.88%) of the efflux pump genes were upregulated at 1/8 MIC of linezolid, indicating that this concentration is optimal for studying efflux pump activity. These findings not only identify 1/8 MIC as optimum concentration for efflux pump studies after linezolid exposure, they also highlight the significant role of efflux pumps in linezolid resistance, providing potential targets for further research on efflux pumps in clinical isolates of M. tuberculosis.
2025-02-20 | GSE288598 | GEO
Project description:Previous studies have shown that the MpeR transcriptional regulator produced by Neisseria gonorrhoeae represses expression of mtrF, which encodes a putative inner membrane protein that works with the MtrC-MtrD-MtrE efflux pump to allow gonococci to resist high levels of multiple hydrophobic antimicrobials. Regulation of mpeR has been reported to occur by an iron-dependent mechanism involving Fur (Ferric uptake regulator). Collectively, these observations suggest the presence of an interconnected regulatory system in gonococci that modulates expression of drug efflux pump protein-encoding genes in an iron-responsive manner. Herein, we describe this connection and report that levels of gonococcal resistance to a substrate of the mtrCDE-encoded efflux pump can be modulated by MpeR and the availability of free iron. Using microarray analysis, we found that the mtrR gene, which encodes the direct transcriptional repressor (MtrR) of mtrCDE, is an MpeR-repressed determinant in the late-logarithmic phase of growth when free iron levels would be reduced due to bacterial consumption. MpeR-mediated repression of mtrR appeared to be direct, as judged by DNA-binding analyses, and was enhanced by conditions of iron-limitation, which resulted in increased expression of the mtrCDE efflux pump operon. Taken together, our results indicate that both genetic and physiologic parameters can influence expression of the mtr efflux system and that these can modulate levels of gonococcal susceptibility to efflux pump substrates.
2012-04-04 | GSE32717 | GEO
Project description:MepR is a substrate-responsive repressor of mepR and mepA, which encode itself and a MATE family multidrug efflux pump. Microarray analyses of Staphylococcus aureus SH1000 and its mepR-disrupted derivative revealed changes in expression of many genes in addition to mepR and mepA, notably several involved in virulence Keywords: Staphylococcus aureus, MATE efflux pump, MepR
2009-07-01 | GSE10033 | GEO
Project description:Previous studies have shown that the MpeR transcriptional regulator produced by Neisseria gonorrhoeae represses expression of mtrF, which encodes a putative inner membrane protein that works with the MtrC-MtrD-MtrE efflux pump to allow gonococci to resist high levels of multiple hydrophobic antimicrobials. Regulation of mpeR has been reported to occur by an iron-dependent mechanism involving Fur (Ferric uptake regulator). Collectively, these observations suggest the presence of an interconnected regulatory system in gonococci that modulates expression of drug efflux pump protein-encoding genes in an iron-responsive manner. Herein, we describe this connection and report that levels of gonococcal resistance to a substrate of the mtrCDE-encoded efflux pump can be modulated by MpeR and the availability of free iron. Using microarray analysis, we found that the mtrR gene, which encodes the direct transcriptional repressor (MtrR) of mtrCDE, is an MpeR-repressed determinant in the late-logarithmic phase of growth when free iron levels would be reduced due to bacterial consumption. MpeR-mediated repression of mtrR appeared to be direct, as judged by DNA-binding analyses, and was enhanced by conditions of iron-limitation, which resulted in increased expression of the mtrCDE efflux pump operon. Taken together, our results indicate that both genetic and physiologic parameters can influence expression of the mtr efflux system and that these can modulate levels of gonococcal susceptibility to efflux pump substrates. two strains, two growth phases, three replicates each.
2012-04-03 | E-GEOD-32717 | biostudies-arrayexpress
Project description:Multidrug (MDR) efflux pumps are ancient and conserved molecular machineries with relevant roles in different aspects of the bacterial physiology, besides antibiotic resistance. In the case of the environmental opportunistic pathogen Pseudomonas aeruginosa, it has been shown that overexpression of different efflux pumps is linked to the impairment of the quorum sensing (QS) response. Nevertheless, the causes of such impairment are different for each analyzed efflux pump. Herein, we performed an in-depth analysis of the QS-mediated response of a P. aeruginosa antibiotic resistant mutant that overexpresses MexAB-OprM. Although previous work claimed that this efflux pump extrudes the QS signal 3-oxo-C12-HSL, we show otherwise. Our results evidence that the observed attenuation in the QS response when overexpressing this pump is related to an impaired production of alkyl quinolone QS signals, likely prompted by the reduced availability of one of their precursors, the octanoate. Together with previous studies, this indicates that, although the consequences of overexpressing efflux pumps are similar (impaired QS response), the underlying mechanisms are different. This ‘apparent redundancy' of MDR efflux systems can be understood as a P. aeruginosa strategy to keep the robustness of the QS regulatory network and modulate its output in response to different signals.
2021-10-25 | GSE153996 | GEO