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ChronosAntibiotics SIGNED

Exploring the bacterial cell cycle to re-sensitize antibiotic-resistant bacteria

Total Cost €

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EC-Contrib. €

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Partnership

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Project "ChronosAntibiotics" data sheet

The following table provides information about the project.

Coordinator
UNIVERSIDADE NOVA DE LISBOA 

Organization address
address: CAMPUS DE CAMPOLIDE
city: LISBOA
postcode: 1099 085
website: n.a.

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 Portugal [PT]
 Total cost 2˙533˙500 €
 EC max contribution 2˙533˙500 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-COG
 Funding Scheme ERC-COG
 Starting year 2018
 Duration (year-month-day) from 2018-03-01   to  2023-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSIDADE NOVA DE LISBOA PT (LISBOA) coordinator 2˙533˙500.00

Map

 Project objective

Over the next 35 years, antibiotic resistant bacteria are expected to kill more than 300 million people. The need to find alternative strategies for antimicrobial therapies remains a global challenge with several bottlenecks in the antibiotic discovery process. Using Staphylococcus aureus, the most common multidrug-resistant bacterium in the European Union and an excellent model organism for cell division in cocci, we propose: (i) to find new pathways to re-sensitize resistant bacteria. Bacteria undergo major morphology changes during the cell cycle. We hypothesize that these changes generate windows of opportunity during which bacteria are more susceptible or more tolerant to the action of antibiotics. We will identify key regulators of the cell cycle in order to manipulate the duration of windows of opportunity for the action of existing antibiotics. (ii) to develop new fluorescence-based reporters for whole-cell screenings of antimicrobial compounds with new modes of action, including compounds that arrest or delay the cell cycle; compounds that target non-essential pathways that are required for expression of resistance against existing antibiotics and therefore can be used as synergistic drugs for combination therapies; compounds that inhibit the production of virulence factors and compounds that revert persister states that are phenotypically resistant to antibiotics. (iii) to unravel new modes of action of antibiotics by using the constructed reporter strains as powerful tools to learn how antibiotics act at the single cell level. Over the past years, my group has become expert on the biology of S. aureus, has constructed powerful biological tools to study cell division and synthesis of the cell surface and has studied mechanisms of action of various antimicrobial compounds. We are therefore in a privileged position to quickly unravel the function of new players in the bacterial cell cycle and simultaneously contribute to accelerate antibiotic discovery.

 Publications

year authors and title journal last update
List of publications.
2019 João M. Monteiro, Gonçalo Covas, Daniela Rausch, Sérgio R. Filipe, Tanja Schneider, Hans-Georg Sahl, Mariana G. Pinho
The pentaglycine bridges of Staphylococcus aureus peptidoglycan are essential for cell integrity
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-019-41461-1
Scientific Reports 9/1 2019-11-12
2019 Nathalie T. Reichmann, Andreia C. Tavares, Bruno M. Saraiva, Ambre Jousselin, Patricia Reed, Ana R. Pereira, João M. Monteiro, Rita G. Sobral, Michael S. VanNieuwenhze, Fábio Fernandes, Mariana G. Pinho
SEDS–bPBP pairs direct lateral and septal peptidoglycan synthesis in Staphylococcus aureus
published pages: 1368-1377, ISSN: 2058-5276, DOI: 10.1038/s41564-019-0437-2
Nature Microbiology 4/8 2019-11-12

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