Elucidating microbial resistance

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 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.