Summary of Study ST002131
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001349. The data can be accessed directly via it's Project DOI: 10.21228/M8BM53 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002131 |
| Study Title | Discovery and characterization of virulence associated functional metabolites in Escherichia coli based on functional metabolomics strategy（pellets metabolomics-2） |
| Study Summary | Bacterial metabolites are substrates of virulence factors of uropathogenic Escherichia coli (UPEC), but the mechanism underlying the role of functional metabolites in bacterial virulence from the perspective of small molecular metabolism is unclear. In the present study, we used a strategy of functional metabolomics integrated with bacterial genetics in attempt to decipher the mechanism of virulence formation in Escherichia coli (E. coli) from the viewpoint of small molecule metabolism. We identified the virulence-associated metabolome via analysis of the primary metabolome of the pathogenic UTI89 strain and the non-pathogenic MG1655 strain. Then, the iron-mediated virulence associated metabolome was identified by an iron fishing strategy. Also, the mechanism of siderophores in regulating pathogenicity in different environments was explored by investigating the effect of iron on siderophore biosynthesis. Finally, by knocking out genes related to siderophore biosynthesis, siderophore transport and iron utilization, siderophores dependent iron-regulating virulence associated metabolome, including 18 functional metabolites, was identified and verified to be involved in the regulation of bacterial virulence. Based on this we found that these functional metabolites regulated the virulence of E. coli by targeting multiple metabolic pathways in an iron-siderophores dependent manner. Moreover, a quantitative proteomics approach was implemented to further elucidate the mechanism of functional metabolites and functional proteins in modulating bacterial virulence. And our findings demonstrated that functional proteins regulated the virulence of E. coli by mediating iron binding, iron-siderophore transmembrane transport, and the biosynthesis and expression of functional metabolites. Interestingly, we found that functional metabolites enhance the virulence of E. coli by specifically modulating the key metabolic pathways involved in purine metabolism, proline metabolism, arginine metabolism and pyrimidine metabolism. Taken together, our study identified for the first time 18 functional metabolites regulating the of E. coli virulence, greatly enriching our understanding of the mechanism of functional metabolites that regulate the E. coli virulence by targeting primary metabolism, which will largely contribute to the development of new strategies to target virulence-based diagnosis and therapy of infections caused by different pathogens. |
| Institute | Shanghai Center for Systems Biomedicine, Shanghai Jiaotong University |
| Last Name | Lu |
| First Name | Haitao |
| Address | 800 Dongchuan RD. Minhang District, Shanghai, Shanghai, 200240, China |
| haitao.lu@sjtu.edu.cn | |
| Phone | 15221478139 |
| Submit Date | 2022-03-25 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-04-20 |
| Release Version | 1 |
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Factors:
Subject type: Bacteria; Subject species: Escherichia coli (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA204512 | fur-0-2P | No iron supplementation |
| SA204513 | fur-0-1P | No iron supplementation |
| SA204514 | fur-0-4P | No iron supplementation |
| SA204515 | fur-0-3P | No iron supplementation |
| SA204516 | fur-0-6P | No iron supplementation |
| SA204517 | fur-0-5P | No iron supplementation |
| SA204518 | fyuA-0-3P | standard growth conditions |
| SA204519 | fyuA-0-4P | standard growth conditions |
| SA204520 | fyuA-0-6P | standard growth conditions |
| SA204521 | fyuA-0-2P | standard growth conditions |
| SA204522 | fyuA-0-5P | standard growth conditions |
| SA204523 | fyuA-0-1P | standard growth conditions |
| SA204524 | ybtP-0-5P | standard growth conditions |
| SA204525 | ybtP-0-6P | standard growth conditions |
| SA204526 | ybtP-0-4P | standard growth conditions |
| SA204527 | ybtP-0-3P | standard growth conditions |
| SA204528 | ybtP-0-2P | standard growth conditions |
| SA204529 | ybtQ-0-1P | standard growth conditions |
| SA204530 | ybtQ-0-2P | standard growth conditions |
| SA204531 | ybtQ-0-6P | standard growth conditions |
| SA204532 | ybtQ-0-5P | standard growth conditions |
| SA204533 | ybtQ-0-4P | standard growth conditions |
| SA204534 | ybtQ-0-3P | standard growth conditions |
| SA204535 | ybtP-0-1P | standard growth conditions |
| Showing results 1 to 24 of 24 |
