MIX-Effectors SIGNED
T6SS MIX-effectors: secretion, activities and use as antibacterial treatment
Total Cost €
0EC-Contrib. €
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Project "MIX-Effectors" data sheet
The following table provides information about the project.
| Coordinator |
TEL AVIV UNIVERSITY
Organization address contact info |
| Coordinator Country | Israel [IL] |
| Total cost | 1˙484˙375 € |
| EC max contribution | 1˙484˙375 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2016-STG |
| Funding Scheme | ERC-STG |
| Starting year | 2017 |
| Duration (year-month-day) | from 2017-02-01 to 2022-01-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | TEL AVIV UNIVERSITY | IL (TEL AVIV) | coordinator | 1˙484˙375.00 |
Map
Project objective
Bacteria use various mechanisms to combat competitors and colonize new niches. The Type VI Secretion System (T6SS), a contact-dependent protein delivery apparatus, is a widespread, recently discovered machine used by Gram-negative bacteria to target competitors. Its toxicity is mediated by secreted proteins called effectors, yet the identity of many effectors, the mechanism of secretion of different effector classes, and their toxic activities remain largely unknown. I recently uncovered a widespread class of T6SS effectors that share a domain called MIX. MIX-effectors are polymorphic proteins carrying various toxin domains, many of which with unknown activities. Many bacterial pathogens have acquired resistance to contemporary antibiotic treatments, becoming a public health threat and necessitating the development of novel antibacterial strategies. Thus, as a relatively untapped antibacterial system, studying the T6SS and its MIX-effectors presents a double incentive: 1) previously uncharacterized antibacterial activities of MIX-effectors can illuminate novel cellular targets for antibacterial drug development; 2) the T6SS machinery can be used as a novel toxin delivery platform to combat multi-drug resistant bacterial infections, using polymorphic MIX-effectors. In this proposal, I will focus on T6SS MIX-effectors and elucidate their activities, mechanism of secretion, and utilization as antibacterial agents, by combining microbiology, molecular biology, genetic, biochemical, and proteomic approaches. Specifically, the goal of this proposal is to utilize T6SSs and MIX-effectors to develop a novel T6SS-based, antibacterial therapeutic platform in which a nonpathogenic bacterium will be engineered to carry a T6SS that can secrete a diverse repertoire of polymorphic antibacterial MIX-effectors. This innovative platform has several advantages over current antibacterial strategies, and can be used as an adjustable tool to combat multi-drug resistant bacteria.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2020 |
Chaya M. Fridman, Kinga Keppel, Motti Gerlic, Eran Bosis, Dor Salomon A comparative genomics methodology reveals a widespread family of membrane-disrupting T6SS effectors published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-020-14951-4 |
Nature Communications 11/1 | 2020-03-05 |
| 2019 |
Biswanath Jana, Dor Salomon Type VI secretion system: a modular toolkit for bacterial dominance published pages: , ISSN: 1746-0913, DOI: 10.2217/fmb-2019-0194 |
Future Microbiology | 2019-11-28 |
| 2019 |
Biswanath Jana, Chaya M. Fridman, Eran Bosis, Dor Salomon A modular effector with a DNase domain and a marker for T6SS substrates published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-11546-6 |
Nature Communications 10/1 | 2019-09-06 |
| 2019 |
Rotem Benâ€Yaakov, Dor Salomon The regulatory network of Vibrio parahaemolyticus type VI secretion system 1 published pages: 2248-2260, ISSN: 1462-2912, DOI: 10.1111/1462-2920.14594 |
Environmental Microbiology Volume21, Issue7 July 2019 | 2019-08-29 |
| 2017 |
Ann Ray, Nika Schwartz, Marcela de Souza Santos, Junmei Zhang, Kim Orth, Dor Salomon Type VI secretion system MIXâ€effectors carry both antibacterial and antiâ€eukaryotic activities published pages: 1978-1990, ISSN: 1469-221X, DOI: 10.15252/embr.201744226 |
EMBO reports 18/11 | 2019-06-13 |
| 2018 |
Dor Salomon MIX-Effectors – T6SS MIX-effectors: secretion, activities and use as antibacterial treatment – ERC published pages: 9-11, ISSN: 2398-7073, DOI: 10.21820/23987073.2018.12.9 |
Impact 2018/12 | 2019-04-03 |
| 2018 |
Yasmin Dar, Dor Salomon, Eran Bosis The Antibacterial and Anti-Eukaryotic Type VI Secretion System MIX-Effector Repertoire in Vibrionaceae published pages: 433, ISSN: 1660-3397, DOI: 10.3390/md16110433 |
Marine Drugs 16/11 | 2019-02-25 |
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