Trade-off Between Resistance and Persistence in High Cell Density Escherichia Coli Cultures
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1062516 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR27462700_1.fastq.gz | Fastqsanger.gz | |||
| SRR27462700_2.fastq.gz | Fastqsanger.gz | |||
| SRR27462901_1.fastq.gz | Fastqsanger.gz | |||
| SRR27462901_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 511 |
Similar Datasets
Project description:Microbes experience high cell density in many environments that come with diverse resource limitations and stresses. However, high density physiology remains poorly understood. We utilized well-controlled culturing systems to grow wild-type and metabolically engineered Escherichia coli strains into high cell densities (50–80 g Cdry cell weight L-1) and explore the associated transcriptional dynamics. Knowledge-enriched machine-learning-based analytics reveal distinct stress-related gene expression patterns that are consistent with a fundamental trade-off between resistance and persistence. We suggest that this trade-off explains observed growth arrests in high-density cultures and that it results from the disruption of cellular homeostasis, due to reallocation of limited cellular resources from resistance functions towards maintenance requirements of engineered production pathways. This study deepens our understanding of high-density physiology and demonstrates its importance to fundamental biomanufacturing challenges.
2025-06-01 | GSE252784 | GEO
Project description:The evolutionary transition of multicellular life initially involves growth in groups of undifferentiated cells followed by differentiation into soma and germ-like cells. This is facilitated by trade-offs between traits determining survival and reproduction, favoring the coexistence of cells with extreme trait values and a convex trade-off curve as the multicellular state dominates. However, these transitions remain poorly characterized at the ecological and genetic level. Here, we studied the evolution of cell groups in ten isogenic lines of the unicellular green algae Chlamydomonas reinhardtii with prolonged exposure to a rotifer predator. We confirmed that this trait was heritable and characterized by a convex trade-off curve between reproduction and survival. Identical mutations evolved in all cell group isolates which were linked to survival and reducing associated cell costs. Overall, we show that just 500 generations of predator selection is sufficient to lead to a convex trade-off and incorporate evolved changes into the prey genome.
2021-02-13 | GSE166685 | GEO
Project description:The Baculovirus Expression Vector System (BEVS) is highly valued in vaccine development, protein engineering, and drug metabolism research due to its biosafety, operational convenience, rapid scalability, and capacity for self-assembling virus-like particles. However, increasing cell density at the time of inoculation severely compromises the production capacity of BEVS, resulting in the “cell density effect”. This study aimed to explore the mechanisms of the cell density effect through time-series analysis of transcriptomes and proteomes, with the goal of overcoming or alleviating the decline in productivity caused by increased cell density. The dynamic analysis of the omics of High Five cells under different CCI (cell density at infection) conditions showed that the impact of the “cell density effect” increased over time, particularly affecting genetic information processing, error repair, protein expression regulation, and material energy metabolism. Omics analysis of the growth stage of High Five cells showed that after 36 h of culture (cell density of about 1×106 cells/mL), the expression of ribosome-related proteins decreased, resulting in a rapid decrease in protein synthesis capacity, which was a key indicator of cell aging. Senescence verification experiments showed that cells began to show obvious early aging characteristics after 36 h, resulting in a decrease in the host cell’s ability to resist stress. Overexpression and siRNA inhibition studies showed that the ndufa12 gene was a potential regulatory target for restricting the “cell density effect”. Our results suggested that stress-induced premature senescence in High Five cell cultures, resulting in reduced energy metabolism and protein synthesis capabilities, was a critical factor contributing to cell density effects, and ultimately affecting virus production. In conclusion, this study provided new insights into managing virus production limitations due to cell density effects and offered innovative strategies to mitigate the adverse effects of cellular aging in biomanufacturing technologies.
2024-10-31 | PXD057379 |
Project description:Activation of immunity via LPS injection causes an energetic trade-off with the somatic maintenance program of homeothermy, resulting in hypometabolism and hypothermia. To better understand the pathways involved in this trade-off, genome-wide expression profiling was performed on livers of mice housed at 2 different ambient temperatures (22°C and 30°C) with tissue collected at several timepoints post-LPS injection (0, 4, 12, 24hours). Our analysis revealed that regardless of ambient temperature, LPS reprograms host metabolism with distinct metabolic programs engaged to support entry and recovery from the hypometabolic state.
2019-03-07 | GSE114473 | GEO
Project description:Over expression of recombinant proteins is known to cause a metabolic burden to the host cells which leads to down regulation of both growth rates and protein expression. Most studies in this regard have been conducted in low density shake flask cultures which does not capture the essential features of an industrial scale bioprocess. In the present work we studied the transcriptomic profiling at different specific growth rates while expressing the recombinant human interferon beta in fed batch cultures with complex media. These conditions mimicked the industrial fermentations for recombinant proteins.
2011-04-07 | GSE28412 | GEO
Project description:The Baculovirus Expression Vector System (BEVS) is highly valued in vaccine development, protein engineering, and drug metabolism research due to its biosafety, operational convenience, rapid scalability, and capacity for self-assembling virus-like particles. However, increasing cell density at the time of inoculation severely compromises the production capacity of BEVS, resulting in the “cell density effect”. This study aimed to explore the mechanisms of the cell density effect through time-series analysis of transcriptomes and proteomes, with the goal of overcoming or alleviating the decline in productivity caused by increased cell density. The dynamic analysis of the omics of High Five cells under different CCI (cell density at infection) conditions showed that the impact of the “cell density effect” increased over time, particularly affecting genetic information processing, error repair, protein expression regulation, and material energy metabolism. Omics analysis of the growth stage of High Five cells showed that after 36 h of culture (cell density of about 1×106 cells/mL), the expression of ribosome-related proteins decreased, resulting in a rapid decrease in protein synthesis capacity, which was a key indicator of cell aging. Senescence verification experiments showed that cells began to show obvious early aging characteristics after 36 h, resulting in a decrease in the host cell’s ability to resist stress. Overexpression and siRNA inhibition studies showed that the ndufa12 gene was a potential regulatory target for restricting the “cell density effect”. Our results suggested that stress-induced premature senescence in High Five cell cultures, resulting in reduced energy metabolism and protein synthesis capabilities, was a critical factor contributing to cell density effects, and ultimately affecting virus production. In conclusion, this study provided new insights into managing virus production limitations due to cell density effects and offered innovative strategies to mitigate the adverse effects of cellular aging in biomanufacturing technologies.
2024-12-05 | GSE280032 | GEO
Project description:Background: Variation in locomotor capacity among animals often reflects adaptations to different environments. Despite evidence that physical performance is heritable, the molecular basis of locomotor performance and performance trade-offs remains poorly understood. In this study we identify the genes, signaling pathways, and regulatory processes responsible for the trade-off between burst performance and endurance observed in Xenopus allofraseri, using a transcriptomic approach. Results: We obtained a total of about 121 million paired-end reads from Illumina RNA sequencing and analyzed 218,541 transcripts obtained from a de novo assembly. We identified 109 transcripts with a significant differential expression between endurant and burst performant individuals (FDR ≤ 0.05 and logFC ≥ 2), and blast searches resulted in 103 protein-coding genes. We found major differences between endurant and burst-performant individuals in the expression of genes involved in the polymerization of actin filaments, cellular trafficking, proteoglycans and extracellular proteins secreted, lipid metabolism, mitochondrial activity and regulators of signaling cascade. Remarkably, we revealed transcripts isoforms of key genes with function in metabolism, apoptosis, nuclear export and as transcriptional corepressor, expressed in either burst-performant or endurant individuals. Lastly, we find two up-regulated transcripts in burst-performant individuals that correspond to the expression of myosin-binding protein C fast-type (mybpc2). This suggests the presence of mybpc2 homoeologs and may have been favored by selection to permit fast and powerful locomotion. Conclusion: Locomotor performance trade-off in Xenopus allofraseri can be attributed to the differential expression of genes belonging to the different pathways of calcium signaling, endoplasmic reticulum stress response and striated muscle contraction, but also attributed to the use of alternative splicing and regulatory processes. Ultimately, our transcriptomic analysis offers new perspectives for future analyses of the role of single nucleotide variants, homoeology and alternative splicing in the evolution of locomotor performance trade-offs.
2021-01-31 | GSE157915 | GEO
Project description:Assessing the effects of transcription factor knockouts on growth in high-density fed-batch cultures
| PRJNA915398 | ENA