ICADIGE

The Integron Cassette Dynamics and the Integrase Gene Expression

 Coordinatore INSTITUT PASTEUR 

 Organization address address: RUE DU DOCTEUR ROUX 25-28
city: PARIS CEDEX 15
postcode: 75724

contact info
Titolo: Dr.
Nome: Marie-Laure
Cognome: Rosso
Email: send email
Telefono: +33 1 44 38 95 26
Fax: +33 1 40 61 39 40

 Nazionalità Coordinatore France [FR]
 Totale costo 193˙594 €
 EC contributo 193˙594 €
 Programma FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call FP7-PEOPLE-2011-IEF
 Funding Scheme MC-IEF
 Anno di inizio 2012
 Periodo (anno-mese-giorno) 2012-10-01   -   2014-09-30

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    INSTITUT PASTEUR

 Organization address address: RUE DU DOCTEUR ROUX 25-28
city: PARIS CEDEX 15
postcode: 75724

contact info
Titolo: Dr.
Nome: Marie-Laure
Cognome: Rosso
Email: send email
Telefono: +33 1 44 38 95 26
Fax: +33 1 40 61 39 40

FR (PARIS CEDEX 15) coordinator 193˙594.80

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

data    mutations    integrons    sos    efficient    vivo    bacteria    genes    integrase    responsible    recruitment    resistance    deaths    gene    antimicrobial    ar    evolutionary    aids    plasmids    molecules    worrisome    integron    int    experiments    genetic    cassettes    fight    dynamics    enzyme    parallel    evolution    icadige    times   

 Obiettivo del progetto (Objective)

'Bacterial antimicrobial resistance has become one of the major concerns in modern medicine. It is currently responsible in Europe for 15 times as many deaths as AIDS every year. Not surprisingly this phenomenon is one of the Top Six Health Topics for the eCDC. Bacteria have shown a remarkable evolvability towards resistance. One of the most worrisome mechanisms observed, is the integron, a highly efficient gene-recruitment platform. In addition to rising resistance, there are no encouraging perspectives in the drug discovery field. Thus, containment is the major asset in combating resistance. Nevertheless new and creative approaches are being assessed. A good example is the study of molecules against the integrase. A deep knowledge on the integrase’s activity and its regulation is at the basis of any major achievements in the field. This project aims to better understand integrons and to acquire new knowledge that will ultimately help combat antimicrobial resistance. The first set of experiments will unravel the behaviour of integrons in vivo. By developing a mouse model, we will study the influence of antibiotic therapy in the integrase induction through SOS response in the gut. Further work will be focused on the in vivo integron/plasmid synergy, as single stranded DNA transmission during conjugation can trigger integrase activation in vitro through SOS response. Such interaction is especially worrisome as many resistance plasmids carry resistance integrons.This data will help understand the behaviour of integrons and the dynamics of integrases in their natural environment. Altogether, the results of this project will mean a breakthrough in understanding the evolutionary potential integrons confer to bacteria. This knowledge will definitely help develop efficient tools to fight antimicrobial resistance.'

Introduzione (Teaser)

Antimicrobial resistance (AR) is currently responsible for 15 times as many deaths caused by AIDS every year. EU researchers are investigating one of the microbes' genetic vehicles of resistance, the integron.

Descrizione progetto (Article)

Integrons are highly efficient gene recruitment platforms and are found as part of mobile genetic elements such as plasmids. They are therefore a major force to be reckoned with in the fight against AR. The project ICADIGE (The integron cassette dynamics and the integrase gene expression) has investigated the molecular dynamics of the integron and the enzyme responsible for integration of further genes, integrase.

The researchers worked with the genes and their products that allow insertion of more cassettes. These included the int1 gene that codes for an enzyme that belongs to the integrase family and an attC sequence that flanks cassettes and enables other cassettes to be integrated at the attI site.

To explore the evolutionary possibilities of the integrase protein, the scientists recoded the int1 gene into two alternative yet synonymous genes. Mutations were then subjected to directed evolution experiments. Able to identify frequencies of the different mutations, the researchers also characterised structural data on constraints of the reaction.

By looking at the evolution of the three genes in parallel, ICADIGE has induced elements of convergent and parallel evolution, epistatic interactions where alleles of the mutations masked effects of others, and re-evolution of amino acid residues.

Understanding the elements of AR could lead to the development of molecules that will halt the recombination process that leads to production of new mutations for resistance. Key proteins in the process that have been isolated can be crystallised for further work on their part in AR.

Altri progetti dello stesso programma (FP7-PEOPLE)

SCALE (2009)

Speech Communication with Adaptive Learning

Read More  

SERENDIPITY (2014)

"Serendipity in Science, Technology and Innovation"

Read More  

FOOSAF (2011)

The Application of Modern Proteomic and Metabolomic Methodologies to the Assessment of FOOd SAFety

Read More