Ontology highlight
ABSTRACT:
PROVIDER: PRJNA744907 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15075171.fastq.gz | Fastqsanger.gz | |||
| SRR15075173.fastq.gz | Fastqsanger.gz | |||
| SRR15075175.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Mutations in the rifampicin (Rif)-binding site of RNA polymerase (RNAP) impart antibiotic resistance and inextricably affect transcription initiation, elongation, and termination properties as well. At each step of the transcription cycle, RNAP responds to non-essential transcription factors, signaling molecules, and substrate availability. As such, the non- essential genome and its impact on fitness cost potentially represent an untapped resource for new combination therapies. Using transposon sequencing (Tn-seq), we present a genome- wide analysis of resistance cost in a clinically common rpoB H526Y mutant. Our data show that cost-compounding genes include factors that promote high transcription elongation rate, whereas cost-mitigating genes function in cell wall synthesis and division. We demonstrate that cell wall synthesis and division defects in rpoB H526Y are a consequence of an abnormally high transcription elongation rate, which is further exacerbated by superfluous activity of the uracil salvage pathway and indifference of the mutant RNAP to alarmone ppGpp. Leveraging on this knowledge, we identified drugs that are highly potent against rpoB H526Y and other RifR alleles from the same phenotypic class. Thus, genome-wide analysis of fitness cost of antibiotic resistant mutants should expedite discovery of new combination therapies and delineate cellular pathways that underlie molecular mechanisms of cost.
2021-11-25 | PXD027810 | Pride
Project description:The present study was aimed at analyzing (i) the biological cost of RNA polymerase (rpoB) mutations conferring rifampin resistance on H.pylori, (ii) the relationship between the cost of rpoB mutations and the chromosomal mutaion, (iii) the relationship between the cost of rpoB mutations and the transcription profile of sensitive and resistantrif strains of H.pylori (iv) and rpoB mutations in view of the possible fitness burden associated with resistance to another antibiotics. H.pylori reference strain 26695 was routinely maintained on Columbia agar plates and H. pylori-selective antibiotic mix Dent. Liquid culture was grown in BHI broth. Both plates and broth cultures were incubated at 37C under atmosphere enriched with 5% CO2 for 2-3 days . Mutant strains were selected by culturing H. pylori 26695 on selective plates containing rifampicin. In 5 days resistant colonies were picked up and passed under rifampicin pressure. RNA isolated was reverse transcribed and used to probe H. pylori home-made arrays
2010-11-30 | E-GEOD-25333 | biostudies-arrayexpress
Project description:Antimicrobial resistance (AMR) poses a threat to global health and the economy. Rifampicin resistant Mycobacterium tuberculosis accounts for a third of the global AMR burden. Gaining the upper hand on AMR requires a deeper understanding of the physiology of resistance. AMR often results in the erosion of normal cell function: a fitness cost. Identifying intervention points in the mechanisms underpinning the cost of resistance in M. tuberculosis could play a pivotal role in strengthening future treatment regimens. We used a collection of M. tuberculosis strains providing an evolutionary and phylogenetic snapshot of rifampicin resistance and subjected them to genome-wide transcriptomic and proteomic profiling to identify key perturbations of normal physiology. We found that a rifampicin resistance-conferring mutation in RpoB imparts considerable gene expression changes, many of which are mitigated by a compensatory mutation in RpoC. However, our data also provide evidence for pervasive epistasis: the same resistance mutation imposed a different fitness cost and functionally unrelated changes to gene expression in clinical strains from unrelated genetic backgrounds. Rather than functional changes in specific pathways, our data suggest that the fitness cost of rifampicin resistance stems from a misallocation of resources: the greater the departure from the wild type baseline proteome investment, the greater the fitness cost of rifampicin resistance in a given strain. We summarize these observations in the “Burden of Expression” hypothesis of fitness cost and provide evidence that it can be used for suppressing the emergence of rifampicin resistance.
2021-03-12 | PXD011568 | Pride
Project description:The IncX3 plasmid is a primary vector for disseminating carbapenem resistance globally, yet the chromosomal regulatory mechanisms governing its fitness cost remain poorly understood. Our previous work identified the stringent starvation protein SspA as a modulator of IncX3 plasmid fitness in Escherichia coli via flagellar biosynthesis. Here, we elucidate the global regulatory role of SspA and verify whether its effect is mediated through the master regulator H-NS
2026-08-09 | GSE342412 | GEO
Project description:Bacteria often evolve antibiotic resistance through mutagenesis. However, the processes causing the mutagenesis have not been fully resolved. Here we found that a broad range of ribosome-targeting antibiotics caused mutations through an underexplored pathway. Focusing on the clinically important aminoglycoside gentamicin, we found that the translation inhibitor caused genome-wide premature stalling of RNA polymerase (RNAP) in a loci-dependent manner. Further analysis showed that the stalling was caused by disruption of transcription-translation coupling. Anti-intuitively, the stalled RNAPs subsequently induced lesions to the DNA via transcription-coupled repair. While most of the bacteria were killed by genotoxicity, a small subpopulation acquired mutations via SOS-induced mutagenesis. Given that these processes were triggered shortly after antibiotic addition, resistance rapidly emerged in the population. Our work revealed a new mechanism of action of ribosomal antibiotics, illustrates the importance of dissecting the complex interplay between multiple molecular processes in understanding antibiotic efficacy, and suggests new strategies for countering the development of resistance.
2024-05-15 | GSE267245 | GEO
Project description:We compared the dynamics and mechanisms of resistance development to ceftazidime, meropenem, ciprofloxacin, and ceftolozane-tazobactam in wild-type (PAO1) and mutator (PAOMS, M-bM-^HM-^FmutS) P. aeruginosa. The strains were incubated for 24 h with 0.5 to 64M-CM-^W MICs of each antibiotic in triplicate experiments. The tubes from the highest antibiotic concentration showing growth were reinoculated in fresh medium containing concentrations up to 64M-CM-^W MIC for 7 consecutive days. The susceptibility profiles and resistance mechanisms were assessed in two isolated colonies from each step, antibiotic, and strain. Ceftolozane-tazobactam-resistant mutants were further characterized by whole-genome analysis through RNA sequencing (RNA-seq). The development of high-level resistance was fastest for ceftazidime, followed by meropenem and ciprofloxacin. None of the mutants selected with these antibiotics showed cross-resistance to ceftolozane-tazobactam. On the other hand, ceftolozane-tazobactam resistance development was much slower, and high-level resistance was observed for the mutator strain only. PAO1 derivatives that were moderately resistant (MICs, 4 to 8 ug/ml) to ceftolozane-tazobactam showed only 2 to 4 mutations, which determined global pleiotropic effects associated with a severe fitness cost. High-level-resistant (MICs, 32 to 128 ug/ml) PAOMS derivatives showed 45 to 53 mutations. Major changes in the global gene expression profiles were detected in all mutants, but only PAOMS mutants showed ampC overexpression, which was caused by dacB or ampR mutations. Moreover, all PAOMS mutants contained 1 to 4 mutations in the conserved residues of AmpC (F147L, Q157R, G183D, E247K, or V356I). Complementation studies revealed that these mutations greatly increased ceftolozane-tazobactam and ceftazidime MICs but reduced those of piperacillin-tazobactam and imipenem, compared to those in wild-type ampC. Therefore, the development of high-level resistance to ceftolozane-tazobactam appears to occur efficiently only in a P. aeruginosa mutator background, in which multiple mutations lead to overexpression and structural modifications of AmpC. Mutants of Pseudomonas aeroginosa PAO1 and PAO1 M-bM-^HM-^FmutS against Ceftolozane-tazobactam were generated and analysed using RNA-Seq
2014-06-12 | E-GEOD-58390 | biostudies-arrayexpress
Project description:Bacteria often evolve antibiotic resistance through mutagenesis. However, the processes causing the mutagenesis have not been fully resolved. Here we found that a broad range of ribosome-targeting antibiotics caused mutations through an underexplored pathway. Focusing on the clinically important aminoglycoside gentamicin, we found that the translation inhibitor caused genome-wide premature stalling of RNA polymerase (RNAP) in a loci-dependent manner. Further analysis showed that the stalling was caused by disruption of transcription-translation coupling. Anti-intuitively, the stalled RNAPs subsequently induced lesions to the DNA via transcription-coupled repair. While most of the bacteria were killed by genotoxicity, a small subpopulation acquired mutations via SOS-induced mutagenesis. Given that these processes were triggered shortly after antibiotic addition, resistance rapidly emerged in the population. Our work revealed a new mechanism of action of ribosomal antibiotics, illustrates the importance of dissecting the complex interplay between multiple molecular processes in understanding antibiotic efficacy, and suggests new strategies for countering the development of resistance.
2024-06-24 | GSE240474 | GEO
Project description:The present study was aimed at analyzing (i) the biological cost of RNA polymerase (rpoB) mutations conferring rifampin resistance on H.pylori, (ii) the relationship between the cost of rpoB mutations and the chromosomal mutaion, (iii) the relationship between the cost of rpoB mutations and the transcription profile of sensitive and resistantrif strains of H.pylori (iv) and rpoB mutations in view of the possible fitness burden associated with resistance to another antibiotics.
2010-11-30 | GSE25333 | GEO
Project description:While the evolution of insecticide resistance is often assumed to come with a fitness cost, there are instances where insect populations that acquired resistance fail to show an evolutionary cost to maintaining the trait in the absence of insecticide. In comparing two populations of tea tortrix moth, Adoxophyes honmai, we found the absence of a cost of resistance. We conducted an RNA-seq experiment comparing the midgut tissue in these two populations, one susceptible and one resistant, to explore and identify midgut-specific differences in gene expression. We found upregulation in detoxification enzymes commonly associated with insecticide resistance in the midguts of resistant larvae, but also noted differences in digestive enzyme gene expression. This raised the possibility that insecticide resistance coevolved with enhanced digestive capabilities, potentially offsetting putative costs of resistance. Future studies on fitness costs of resistance may do well to consider other physiological systems and their interactions with direct mechanisms of resistance.
2026-09-01 | GSE288080 | GEO