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| Status |
Public on Feb 20, 2024 |
| Title |
Bacterial single cell RNA-seq unveils cyclic-di-GMP as an antitoxin critical for antibiotic tolerance in biofilm [scRNA-seq] |
| Organisms |
Staphylococcus aureus; Pseudomonas aeruginosa PAO1; Escherichia coli str. K-12 substr. MG1655 |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Biofilms are heterogeneous bacterial communities featured by high persister prevalence, responsible for antibiotic tolerance. However, the mechanisms underlying persister formation within biofilms remained ambiguous. Here, by developing and utilizing a ribosomal RNA depleted bacterial single-cell RNA-seq method, RiboD-mSPLiT, we resolved biofilm heterogeneity and discovered pdeI as a marker gene for persister subgroup within biofilms. Remarkably, our findings elucidated that PdeI upregulates cellular levels of c-di-GMP, which acts as an antitoxin to modulate the toxicity of toxin protein HipH. HipH localizes on nucleoid and functions as a potent DNase, inducing cells into a viable but non-culturable state. Conversely, c-di-GMP interacts with HipH, reducing its genotoxic effects and enabling cells to enter a persister state, resulting in drug tolerance. Importantly, by targeting this toxin-antitoxin system, we repressed drug tolerance in Uropathogenic Escherichia coli infections, offering promising therapeutic strategies against chronic and relapsing infections.
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| Overall design |
we performed a new single-cell library construction method for three species of bacteria: Escherichia coli MG1655, Pseudomonas aeruginosa PAO1, Staphylococcus aureus 25923 and verified the effect of different treatments during library construction on library data. Then we analysed two E.coli single-cell sequencing datas, because we found that by cluster analysis we can find biofilm's marker gene
** The submitter states that the study's data have undergone significant changes and are no longer accurately reflected in SuperSeries GSE239505 [Feb 20, 2024]. The correct data are in SuperSeries GSE260458. **
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| Web link |
https://assets.researchsquare.com/files/rs-3329601/v1/579c700c-8679-4c2a-9ee4-dff08841c51a.pdf?c=1700559269
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| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jul 28, 2023 |
| Last update date |
Mar 01, 2024 |
| Contact name |
Xiaodan Yan |
| E-mail(s) |
2019206500042@whu.edu.cn
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| Phone |
13283874287
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| Organization name |
Wuhan University
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| Department |
Medical Research Institute
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| Street address |
Donghu Road, No. 115, Wuchang District,
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| City |
Wuhan |
| State/province |
Hubei Province |
| ZIP/Postal code |
430071 |
| Country |
China |
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| Platforms (3) |
| GPL26592 |
Illumina NovaSeq 6000 (Escherichia coli str. K-12 substr. MG1655) |
| GPL27158 |
Illumina NovaSeq 6000 (Staphylococcus aureus) |
| GPL28916 |
Illumina NovaSeq 6000 (Pseudomonas aeruginosa PAO1) |
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| Samples (14)
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| GSM7666363 |
EC-3h-ΔΔ, replicate 2, scRNA-seq |
| GSM7666364 |
EC-3h, replicate 1, scRNA-seq |
| GSM7666365 |
EC-3h, replicate 2, scRNA-seq |
| GSM7666366 |
PA-biofilm, replicate 1, scRNA-seq |
| GSM7666367 |
PA-biofilm, replicate 2, scRNA-seq |
| GSM7666368 |
PA-biofilm-ΔΔ, replicate 1, scRNA-seq |
| GSM7666369 |
PA-biofilm-ΔΔ, replicate 2, scRNA-seq |
| GSM7666370 |
SA-3h, replicate 1, scRNA-seq |
| GSM7666371 |
SA-3h, replicate 2, scRNA-seq |
| GSM7666372 |
SA-3h-ΔΔ-replicate 1, scRNA-seq |
| GSM7666373 |
SA-3h-ΔΔ-replicate 2, scRNA-seq |
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| This SubSeries is part of SuperSeries: |
| GSE239505 |
Bacterial single cell RNA-seq unveils cyclic-di-GMP as an antitoxin critical for antibiotic tolerance in biofilm. |
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| Relations |
| BioProject |
PRJNA999602 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE239504_ECOLI_rRNA_and_mRNA_reads.txt.gz |
116.9 Kb |
(ftp)(http) |
TXT |
| GSE239504_PAO1_rRNA_and_mRNA_reads.txt.gz |
132.6 Kb |
(ftp)(http) |
TXT |
| GSE239504_RAW.tar |
1.5 Gb |
(http)(custom) |
TAR (of XLSX) |
| GSE239504_Result_of_correlation_analysis_between_mSPLiT_and_RiboD-mSPLiT.xlsx |
129.3 Kb |
(ftp)(http) |
XLSX |
| GSE239504_Result_of_correlation_analysis_between_scRNA_and_bulk_RNA-seq_.xlsx |
143.3 Kb |
(ftp)(http) |
XLSX |
| GSE239504_SA_rRNA_and_mRNA_reads.txt.gz |
71.2 Kb |
(ftp)(http) |
TXT |
| GSE239504_computational_pipeline_readme.txt |
13.3 Kb |
(ftp)(http) |
TXT |
| GSE239504_scripts.tar.gz |
10.4 Kb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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