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MIX-Effectors SIGNED

T6SS MIX-effectors: secretion, activities and use as antibacterial treatment

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EC-Contrib. €

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Project "MIX-Effectors" data sheet

The following table provides information about the project.

Coordinator
TEL AVIV UNIVERSITY 

Organization address
address: RAMAT AVIV
city: TEL AVIV
postcode: 69978
website: http://www.tau.ac.il/

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 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.

# participants  country  role  EC contrib. [€] 
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
List of publications.
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 Ben‐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 MIX‐effectors carry both antibacterial and anti‐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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