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Understanding the evolution of plasmid-mediated antibiotic resistance in real life scenarios

Objective

Antibiotics are essential tools in modern medicine and are indispensable not only for the treatment of infectious diseases but also to support other key interventions such as surgery and cancer chemotherapy. However, the extensive and inappropriate use of antibiotics has fuelled the spread of resistance mechanisms in pathogenic bacteria, leading to the dawn of a post-antibiotic era. Plasmids play a pivotal role in the evolution of antibiotic resistance (AR) because they drive the horizontal transfer of resistance genes between pathogenic bacteria by conjugation. Some of these plasmid-bacterium associations become particularly successful, creating superbugs that spread uncontrollably in clinical settings. The rise of these clones is mainly constricted because plasmids entail a fitness cost when they arrive in a new bacterial host. This cost can be subsequently alleviated through compensatory adaptation during plasmid-bacterium coevolution. Despite the importance of this cost-compensation dynamic in the evolution of plasmid-mediated AR, it remains completely unexplored in clinical contexts. In this project I plan to bridge this gap by exploring the genetic basis underlying the evolution of plasmid-mediated AR in clinically relevant scenarios. We will study, for the first time, the intra-patient transmission, fitness cost and adaptation of AR plasmids in the gut microbiome of hospitalized patients (obj. 1). We will analyse the molecular mechanisms that determine the success of AR plasmids and bacterial clone associations (obj. 2). Finally, we will develop new technology to test how antibiotic treatments affect AR plasmids dynamics in the gut microbiome at an unprecedentedly high-resolution (obj. 3). This ground-breaking project will allow a new understanding of the evolution of plasmid-mediated AR in real life, opening new research avenues and providing a major step towards meeting one of the central challenges facing our society: controlling the spread of AR.

Call for proposal

ERC-2017-STG
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Host institution

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Address
Calle Serrano 117
28006 Madrid
Spain

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Activity type
Research Organisations
EU contribution
€ 908 791,98

Beneficiaries (2)

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain
EU contribution
€ 908 791,98
Address
Calle Serrano 117
28006 Madrid

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Activity type
Research Organisations
SERVICIO MADRILENO DE SALUD
Spain
EU contribution
€ 588 522,02
Address
Plaza Carlos Trias Bertran 7
28020 Madrid

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Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)