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| Status |
Public on Dec 24, 2023 |
| Title |
RNA polymerase stalling-derived genome instability underlies ribosomal antibiotic efficacy and resistance evolution |
| Organism |
Escherichia coli |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
In bacteria, the precise coordination of DNA replication, transcription and translation is mediated by dynamic interactions among the corresponding macromolecular machineries, playing a pivotal role in maintaining cellular homeostasis. Here we showed that such coordination could be hijacked by ribosome antibiotics to trigger secondary damage predominantly contributing to their efficacy, via a yet overlooked reverse-central-dogma pathway. Through the utilization of a self-establishing transcription dynamics profiling method, complemented by genetic and biochemical approaches, we unveil that the disruption of transcription-translation coupling leads to premature stalling of RNA polymerase (RNAP) at genome scale, subsequently triggering extensive genomic instability. Moreover, a distinct subpopulation exhibits hyperactivation of the SOS response, facilitating an inducible evolutionary path towards genetic resistance characterized by a unique mutation spectrum. Our findings reveal the emergence of secondary drug damage resulting from network disorder, and establish a framework to understand antibiotic efficacy and induced mutagenesis from a systems biology perspective.
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| Overall design |
To investigate the secondary effect of gentamicin treatment, which is transcription elongation chaos and mutagensis, we performed RNA-seq and 3' -end-seq to profile transcription dynamics and genome re-sequencing to identify mutations.
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| Web link |
https://www.nature.com/articles/s41467-024-50917-6
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| Contributor(s) |
Wang T, Zheng Y, Chai R |
| Citation(s) |
39097616 |
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| Submission date |
Jun 06, 2023 |
| Last update date |
Aug 05, 2024 |
| Contact name |
Tianmin Wang |
| E-mail(s) |
wangtm@shanghaitech.edu.cn
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| Organization name |
ShanghaiTech University
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| Department |
School of Life Science and Technology
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| Lab |
Tianmin Wang Lab
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| Street address |
Huaxia Middle Road, 393
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| City |
Shanghai |
| ZIP/Postal code |
201210 |
| Country |
China |
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| Platforms (1) |
| GPL25368 |
Illumina NovaSeq 6000 (Escherichia coli) |
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| Samples (57)
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| GSM7458252 |
Gentamicin, 13 min, RNA-seq, wildtype |
| GSM7458253 |
Gentamicin, 20 min, RNA-seq, wildtype |
| GSM7458254 |
Gentamicin, 40 min, RNA-seq, wildtype |
| GSM7458255 |
Gentamicin, 60 min, RNA-seq, wildtype |
| GSM7458256 |
Gentamicin, 74 min, RNA-seq, wildype |
| GSM7458257 |
Gentamicin, 110 min, RNA-seq, wildtype |
| GSM7458258 |
0 min, RNA-seq, Δmfd |
| GSM7458259 |
Gentamicin, 60 min, RNA-seq, Δmfd |
| GSM7458260 |
Gentamicin, 110 min, RNA-seq, Δmfd |
| GSM7458261 |
0 min, replicate 1, 3'-end-seq, wildtype |
| GSM7458262 |
0 min, replicate 2, 3'-end-seq, wildtype |
| GSM7458263 |
Gentamicin, 6 min, 3'-end-seq, wildtype |
| GSM7458264 |
Gentamicin, 13 min, 3'-end-seq, wildtype |
| GSM7458265 |
Gentamicin, 20 min, 3'-end-seq, wildtype |
| GSM7458266 |
Gentamicin, 40 min, 3'-end-seq, wildtype |
| GSM7458267 |
Gentamicin, 60 min, 3'-end-seq, wildtype |
| GSM7458268 |
Gentamicin, 74 min, 3'-end-seq, wildype |
| GSM7458269 |
Gentamicin, 110 min, 3'-end-seq, wildtype |
| GSM7458270 |
0 min, 3'-end-seq, Δmfd |
| GSM7458271 |
Gentamicin, 60 min, 3'-end-seq, Δmfd |
| GSM7458272 |
Gentamicin, 110 min, 3'-end-seq, Δmfd |
| GSM7458273 |
Gentamicin-induced mutation 1 |
| GSM7458274 |
Gentamicin-induced mutation 2 |
| GSM7458275 |
Gentamicin-induced mutation 3 |
| GSM7458276 |
Gentamicin-induced mutation 4 |
| GSM7458277 |
Gentamicin-induced mutation 5 |
| GSM7458278 |
Gentamicin-induced mutation 6 |
| GSM7458279 |
Gentamicin-induced mutation 7 |
| GSM7458280 |
Gentamicin-induced mutation 8 |
| GSM7458281 |
Gentamicin-induced mutation 9 |
| GSM7458282 |
Gentamicin-induced mutation 10 |
| GSM7458283 |
Gentamicin-induced mutation 11 |
| GSM7458284 |
Gentamicin-induced mutation 12 |
| GSM7458285 |
Gentamicin-induced mutation 13 |
| GSM7458286 |
Gentamicin-induced mutation 14 |
| GSM7458287 |
Gentamicin-induced mutation 15 |
| GSM7458288 |
Gentamicin-induced mutation 16 |
| GSM7458289 |
Gentamicin-induced mutation 17 |
| GSM7458290 |
Gentamicin-induced mutation 18 |
| GSM7458291 |
Gentamicin-induced mutation 19 |
| GSM7458292 |
Gentamicin-induced mutation 20 |
| GSM7458293 |
Gentamicin-induced mutation 21 |
| GSM7458294 |
Gentamicin-induced mutation 22 |
| GSM7458295 |
Gentamicin-induced mutation 23 |
| GSM7458296 |
Gentamicin-induced mutation 24 |
| GSM7458297 |
Gentamicin-induced mutation 25 |
| GSM7458298 |
Gentamicin-induced mutation 26 |
| GSM7458299 |
Gentamicin-induced mutation 27 |
| GSM7458300 |
Gentamicin-induced mutation 28 |
| GSM7458301 |
Gentamicin-induced mutation 29 |
| GSM7458302 |
Gentamicin-induced mutation 30 |
| GSM7458303 |
Gentamicin-induced mutation 31 |
| GSM7458304 |
Gentamicin-induced mutation 32 |
| GSM7458305 |
Gentamicin-induced mutation 33 |
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| Relations |
| BioProject |
PRJNA980634 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE234254_PRSE_end_CPM.xlsx |
146.1 Mb |
(ftp)(http) |
XLSX |
| GSE234254_mutation_info.xlsx |
12.8 Kb |
(ftp)(http) |
XLSX |
| GSE234254_qualified_gene_TPM.csv.gz |
324.2 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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