EVOTAR

Evolution and Transfer of Antibiotic Resistance

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 Obiettivo del progetto (Objective)

'Antibiotics are essential therapeutics in the treatment of bacterial infections. However, the indiscriminate use of antibiotics has led to the emergence of antibiotic resistant bacteria that pose a major threat to human health as options for treating infections by these bacteria have become limited. The evolution, emergence and spread of antibiotic resistance genes are still only poorly understood and expanding our knowledge on these aspects will provide novel leads to combat the emergence of antibiotic resistance.

The EvoTAR consortium gathers a multi-disciplinary group of leading European researchers in the fields of antibiotic resistance, microbial genomics and mathematical modelling. In addition, three research-intensive SMEs participate in EvoTAR, two of which are involved in the development of novel approaches to minimize the emergence and spread of antibiotic resistance.

The purpose of EvoTAR is to increase the understanding of the evolution and spread of antibiotic resistance in human pathogens. EvoTAR will characterise the human reservoir of antibiotic resistance genes (“the resistome”) by investigating the dynamics and evolution of the interaction between resistant and non-resistant bacteria from the human microbiome and the interrelations of the human resistome with non-human reservoirs of resistance genes. Novel methods will be used to quantify resistance transfer under controlled conditions in gene exchange communities. Mathematical modelling will be applied to predict gene flow between different reservoirs and to predict future resistance trends. Novel in vitro and in vivo models will allow the study of the efficacy of novel therapeutics aimed at reducing selection and spread of antibiotic resistance.

The EvoTAR project will generate novel insights into the evolution and spread of antibiotic resistance genes and thereby create opportunities for the development of novel interventions to curb the rising tide of antibiotic resistance in human pathogens.'

Introduzione (Teaser)

Understanding the dynamics of microbial communities and the evolution of the antibiotic resistance is critical for devising novel intervention strategies.

Descrizione progetto (Article)

Antibiotics are an invaluable weapon against bacterial infections. However, their injudicious use has led to the emergence of bacterial resistance, limiting treatment options and posing a major threat to human health. Since the evolution, emergence and spread of antibiotic resistance genes are poorly understood phenomena, we urgently need to expand our knowledge on these aspects.

To address this issue, the EU-funded http://www.evotar.eu/ (EVOTAR) (Evolution and transfer of antibiotic resistance) project has brought together multi-disciplinary experts across Europe to provide mechanistic insight into the evolution and spread of antibiotic resistance in human pathogens. The consortium will characterise the human reservoir of antibiotic resistance genes and investigate the dynamics and evolution of the interaction between resistant and non-resistant bacteria.

An antibiotic resistance determinants catalogue has been created in which several hundred antibiotic resistance genes have been annotated so far. Interestingly, researchers have identified resistance genes in commensal bacteria which expand in terms of relative abundance and diversity during hospitalisation in the intensive care unit. To assess the relevance of each individual resistance gene and its transferability, the consortium has established functional genomics and metagenomic approaches in combination with bioinformatics pipelines. In addition they produced a customised gene capture platform of 81 000 targets that offers enhanced detection of sequences involved in antimicrobial resistance and transferability.

To address the fitness and epidemiology of antibiotic resistance, the consortium has developed phylogenomic and modelling approaches based on membrane computing, to describe evolution and spread of resistance. Significant efforts have also gone into the development of compounds that reduce antibiotic residues in the gut after antibiotic treatment thereby reducing the selection of antibiotic resistance in the gut and into the identification of natural inhibitors of bacterial conjugation as a means of halting the transmission of resistance.

Currently scientists are in the process of mimicking the natural transfer of resistance genes in controlled microcosms. This will greatly increase our understanding of the mechanisms by which antibiotic resistance gene transfer takes place in nature.

Taken together, the EVOTAR findings will provide invaluable insight into which reservoirs are important sources for the antibiotic resistance genes in human pathogens. The information on the evolution, transfer and emergence of these genes is anticipated to enable the prediction of future resistance trends.