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.
Antibiotics are one of the most apparent success stories of modern medicine and have saved the lives of countless people that suffered from bacterial infections. However, the use of antibiotics has also led to the emergence of antibiotic resistance in bacteria. The development of antibiotic resistance and the distribution of resistant bacteria throughout the biosphere is caused by a decades-long selection process through the application of antibiotics in humans, and animals.
The emergence of antibiotic resistant pathogens is a major threat to human health as therapeutic options for treating infections by antibiotic-resistant bacteria are increasingly limited. Indeed, infections due to antibiotic-resistant bacteria are a major cause of morbidity and mortality in both hospitals and the wider community throughout the world. Prudent use of antibiotics is a logical and necessary step to decelerate resistance development, but this may not completely stop the spread of antibiotic resistance among human pathogens. Antibiotic resistance is a natural biological phenomenon with many facets that are still poorly understood: what are important reservoirs of antibiotic resistance? How do resistant and non-resistant bacteria interact in these reservoirs? Which conditions promote the evolution and transfer of resistance? Expanding our knowledge on these aspects will provide novel leads to combat the emergence of antibiotic resistance.
EvoTAR aims to 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 environmental, animal and food 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, consequently, to make a prognosis of future resistance trends. Novel in vitro and in vivo models of antibiotic resistance evolution and transfer will allow the study of the efficacy of novel intervention approaches aimed at reducing selection and spread of antibiotic resistance
EvoTAR will examine evolution and transfer of antibiotic resistance at different scales, ranging from the broad scale of metagenomic-based research, to more focused studies on the genomic relatedness and evolution of multiresistant enterococci and ESBL producing Enterobacteriaceae, both of which are important multi-resistant opportunistic pathogens, from different ecological niches. This will provide, for the first time, a deep view of the dynamics of microbial communities and the evolution of the antibiotic resistance in the human microbiome. EvoTAR will also monitor shifts in the population structure and overall gene content, triggered by antibiotic therapy, among enterococci and Enterobacteriaceae populations to an extent not documented before. EvoTAR will also elucidate which reservoirs are important sources for the antibiotic resistance genes that emerge in these human pathogens.
Transfer studies in controlled microcosms, which are unique in their ambitions and scope, that mimick transfer under natural conditions, will greatly increase our understanding of the mechanisms by which antibiotic resistance gene transfer takes place in nature and will identify extensive gene exchange networks that are proposed to exist between bacteria.
In vitro adaptive evolution experiments will provide a much broader understanding on the emergence of genes conferring high-level antibiotic resistance than is currently documented. In combination with generic models and methods, this will yield a detailed description of the probability and rate of emergence and spread of resistance-conferring genes and mutations under various environmental conditions and in different genetic backgrounds, will bring the fields of predictive epidemiology and evolution radically forward and will allow a forward-looking analysis of currently circulating resistance genes and allow the prediction of future resistance trends.
In the EvoTAR project we will specifically determine the efficacy of two novel intervention methods aimed at (i) eliminating residual antibiotics that reach the colon or (ii) inhibiting transfer of resistance genes between microorganisms of the commensal flora. The outcome of these two approaches, as well as the results of the entire EvoTAR research programme, will open up avenues for the clinical application of novel intervention approaches aimed at minimizing the emergence and spread of antibiotic resistance genes in human pathogens and in the development of research systems for the discovery and development of additional intervention approaches.