SPECRESEVO

Specificity of Antibiotic Resistance Evolution

 Coordinatore EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZURICH 

 Organization address address: Raemistrasse 101
city: ZUERICH
postcode: 8092

contact info
Titolo: Prof.
Nome: Martin
Cognome: Ackermann
Email: send email
Telefono: +41 44 632 69 28

 Nazionalità Coordinatore Switzerland [CH]
 Totale costo 184˙709 €
 EC contributo 184˙709 €
 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) 2012-03-01   -   2014-02-28

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZURICH

 Organization address address: Raemistrasse 101
city: ZUERICH
postcode: 8092

contact info
Titolo: Prof.
Nome: Martin
Cognome: Ackermann
Email: send email
Telefono: +41 44 632 69 28

CH (ZUERICH) coordinator 184˙709.40

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 Word cloud

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

antibiotic    genotypes    background    experimental    mutations    drive    evolution    microbial    health    environments    bacteria    isolated    antibiotics    related    specificity    compensatory    spread    resistant    absence    evolutionary    mutation    mechanisms    fitness    specresevo    genetic    bacterial    resistance    minimise    problem   

 Obiettivo del progetto (Objective)

'Bacterial resistance to antibiotics is a major problem for global public health, but we have an incomplete understanding of the evolutionary and genetic factors that drive the spread of resistance. This proposal is motivated by the concept that some of the key processes in resistance evolution depend on the specificity of the genetic mechanisms involved, which is at present unclear. Specificity here refers to variation of the phenotypic effects of mutations across genotypes (epistasis) or environments. I will use a combination of microbial experimental evolution, DNA sequencing and evolutionary genetics to address this problem. My objectives are to: (1) quantify the specificity of antibiotic resistance mutations across different concentrations of a range of antibiotics; (2) identify genetic mechanisms that ameliorate growth defects caused by resistance mutations (compensatory adaptation) in different resistant genotypes in both the presence and absence of antibiotics; (3) test whether compensatory adaptation to the cost of one resistance mutation can also recover the cost of other resistance mutations against the same or other antibiotics. This work will improve our understanding of the genetic and evolutionary factors that drive antibiotic resistance evolution.'

Introduzione (Teaser)

A European study investigated the mechanisms by which antibiotic-resistant bacteria evolve. The genetic determinants of this process could have important implications for the spread of microbial resistance.

Descrizione progetto (Article)

Bacterial resistance to antibiotics is a major hurdle for fighting many infections. Numerous research efforts try to address the problem by identifying novel targets and synthesising new compounds with antimicrobial function.

Equally important, however, is understanding the evolutionary and genetic factors that drive the emergence and spread of resistant pathogens. In this context, the EU-funded 'Specificity of antibiotic resistance evolution' (SPECRESEVO) project set out to elucidate how resistance is affected during evolution and in different environments.

Partners isolated resistant bacteria experimentally using conventional protocols and subjected them to different growth conditions. Additionally, they isolated bacteria with a different history of antibiotic exposure to find that the effect of mutations associated with resistance is largely dependent on the environment and the genetic background. Therefore, we need to understand these mechanisms first before we can predict bacterial spread and minimise antibiotic resistance.

Furthermore, partners studied how resistant bacteria grow in the absence of antibiotic pressure. Resistant bacteria continued to have an increased fitness, compared to normal species, without reverting to drug sensitivity, clearly underscoring the necessity of genetic studies to identify the implicated loci. This competitive fitness was mutation-specific and also depended on the genetic background of the pathogen.

SPECRESEVO work proved the principle that experimental microbial evolution is a valid approach for determining key aspects related to antibiotic resistance. Collectively, the generated information sheds light onto the complex process of resistance-mediated fitness and suggests avenues to prohibit resistant bacterial spread. Long-term, this is expected to improve health care and minimise related costs.

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