NABATIVI

"Novel Approaches to Bacterial Target Identification, Validation and Inhibition"

 Coordinatore UNIVERSITA VITA-SALUTE SAN RAFFAELE 

 Organization address address: Via Olgettina 58
city: MILANO
postcode: 20132

contact info
Titolo: Dr.
Nome: Maria Rosa
Cognome: Pedrazzi
Email: send email
Telefono: +39 02 26434845
Fax: +39 02 26433781

 Nazionalità Coordinatore Italy [IT]
 Totale costo 7˙131˙835 €
 EC contributo 5˙506˙000 €
 Programma FP7-HEALTH
Specific Programme "Cooperation": Health
 Code Call FP7-HEALTH-2007-B
 Funding Scheme CP-FP
 Anno di inizio 2009
 Periodo (anno-mese-giorno) 2009-02-01   -   2013-07-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITA VITA-SALUTE SAN RAFFAELE

 Organization address address: Via Olgettina 58
city: MILANO
postcode: 20132

contact info
Titolo: Dr.
Nome: Maria Rosa
Cognome: Pedrazzi
Email: send email
Telefono: +39 02 26434845
Fax: +39 02 26433781

IT (MILANO) coordinator 610˙529.00
2    UNIVERSITA DEGLI STUDI DI MILANO

 Organization address address: Via Festa Del Perdono 7
city: MILANO
postcode: 20122

contact info
Titolo: Ms.
Nome: Stefania
Cognome: Varotto
Email: send email
Telefono: +39 0250315037
Fax: +39 0250315044

IT (MILANO) participant 699˙600.00
3    THE UNIVERSITY OF NOTTINGHAM

 Organization address address: University Park
city: NOTTINGHAM
postcode: NG7 2RD

contact info
Titolo: Mr.
Nome: Paul
Cognome: Cartledge
Email: send email
Telefono: +44 115 9515679
Fax: +44 115 9513633

UK (NOTTINGHAM) participant 681˙600.00
4    UNIVERSITAET ZUERICH

 Organization address address: Raemistrasse 71
city: ZURICH
postcode: 8006

contact info
Titolo: Prof.
Nome: John
Cognome: Robinson
Email: send email
Telefono: +41 44 635 4242
Fax: +41 44 635 4242

CH (ZURICH) participant 674˙800.00
5    EBERHARD KARLS UNIVERSITAET TUEBINGEN

 Organization address address: GESCHWISTER-SCHOLL-PLATZ
city: TUEBINGEN
postcode: 72074

contact info
Titolo: Prof.
Nome: Gerd
Cognome: Döring
Email: send email
Telefono: +49 7071 2982069
Fax: +49 7071 293011

DE (TUEBINGEN) participant 618˙960.00
6 GREENPHARMA S.A.S FR participant 527˙600.00
7    KDEV EXPLORATORY AB

 Organization address address: NOBELS VAEG 3
city: STOCKHOLM
postcode: 171 77

contact info
Titolo: Ms.
Nome: Eva
Cognome: Montgomerie
Email: send email
Telefono: +468 52484801
Fax: +468 52484800

SE (STOCKHOLM) participant 524˙860.00
8 KOBENHAVNS UNIVERSITET DK participant 522˙880.00
9    POLYPHOR AG

 Organization address address: HEGENHEIMERMATTWEG 125
city: ALLSCHWILL
postcode: 4123

contact info
Titolo: Dr.
Nome: Christian
Cognome: Ludin
Email: send email
Telefono: +41 61 567 16 00
Fax: +41 61 567 16 01

CH (ALLSCHWILL) participant 341˙500.00
10    Fondazione Centro San Raffaele

 Organization address address: Via Olgettina 60
city: Milano
postcode: 20132

contact info
Titolo: Dr.
Nome: Maria Rosa
Cognome: Pedrazzi
Email: send email
Telefono: +39 02 2643 4845
Fax: +39 02 2643 4717

IT (Milano) participant 303˙671.00

Mappa


 Word cloud

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

expertise    antibacterial    bacteria    action    validation    virulence    bacterial    natural    smes    resistance    aeruginosa    pseudomonas    diseases    infections    resistant    model    membrane    morbidity    screened    identification    molecules    infectious    organisms    life    truly    specifically       protegrin    found    mortality    drug    peptide    antibiotic    nabativi    antimicrobial    libraries    relevance    patients    antibiotics    modes    panel    pathogens    genes    caused    compounds    impact    treat    worldwide    discovery    genome   

 Obiettivo del progetto (Objective)

'Despite the advent of the antibiotic era, infectious diseases retain their pre-eminent position as major worldwide causes of morbidity and mortality. This problem has been worsen by the emergence of multi-antibiotic resistant bacteria and the failure of Pharmaceutical company drug discovery programmes to design antibiotics with truly novel modes of action. NABATIVI has put together a unique consortium made of six academic insitutions and three highly recognized SMEs with complementary expertise in the fields of molecular pathogenicity and broad expertise in drug discovery, optimisation, preclinical development. The consortium has been specifically designed to generate new strategies leading to the identification and validation of novel targets for antimicrobials using as model organisms the gram-negatives Pseudomonas aeruginosa and Burkholderia cenocepacia as they are key agents of morbidity and mortality worldwide in a wide range of diseases. The versatility of these model bacteria will enable the results obtained to be extrapolated to other bacterial pathogens. The extensive involvement of SMEs in this consortium will enable the selection of lead compounds against the identified targets from their large libraries of natural and synthetic chemicals which after validation will establish the basis for the development of new classes of antibacterial drugs. This will result in a reduction in the incidence and improvement of the treatment of infections caused by these organisms with a direct impact on the quality of life and the life expectancy of the affected risk patient populations.'

Introduzione (Teaser)

Infectious diseases caused by opportunistic pathogens such as Pseudomonas aeruginosa, continue to be a serious cause of morbidity worldwide. The emerging antibiotic resistance is only exacerbating the situation, necessitating the development of antibiotics with truly novel modes of action.

Descrizione progetto (Article)

Over the past forty years, the antibiotics that have entered the market represent mere modifications of existing molecules. To address antimicrobial drug resistance, the EU-funded ?Novel approaches to bacterial target identification, validation and inhibition? (http://www.nabativi.org (NABATIVI)) project was initiated. Researchers worked on selecting lead compounds for future development of a new class of antibiotics to treat infections caused by resistant P. aeruginosa strains.

To identify and validate novel drug targets, scientists screened P. aeruginosa genome and identified essential and virulence targets (genes) as candidates for the development of antibacterials. Targeted mutagenesis experiments and validation in cell and animal models helped identify virulence genes and factors implicated in infection. Interestingly, some targets were found to play key roles in regulating cellular processes linked to P. aeruginosa pathogenesis. The clinical relevance of some of these genes was verified through genome sequencing across a panel of different bacterial isolates. Furthermore, comparative analysis with additional bacterial species resulted in a panel of targets with a global relevance.

For the selection of compounds with antibacterial activity, researchers screened natural products and chemical libraries against specifically selected targets. They also developed novel inhibitors using peptide nucleic acid delivery. A number of extracts and molecules have been found to inhibit some of these targets.

Natural antimicrobial peptide protegrin I was found to bind to the outer membrane protein and interfere with membrane biosynthesis. One attractive protegrin I homologue after toxicity evaluation and in vivo efficacy studies, was envisaged for pulmonary administration as a possible therapeutic approach. This compound is currently being developed and commercialised to treat patients suffering from P. aeruginosa infections.

Given that nearly two thirds of the hospital-associated infections could be prevented with novel antibiotics, the potential socioeconomic impact of the NABATIVI deliverables is enormous. With respect to chronically infected cystic fibrosis patients, new therapies would undoubtedly prove beneficial compared to standard treatments.

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