The evolution of antibiotic resistance: integrating molecular mechanisms of resistance and evolutionary context

Obiettivo

"The evolution of antibiotic resistance poses an important threat to human health and welfare. Antibiotic resistance is accompanied by fitness costs that have been shown to play a key role in the spread of resistance. These costs are variable, but the underlying ecological and genetic causes of this variation remain obscure. Unfortunately, bacteria can adapt to the cost of resistance by compensatory mutations, and this permits resistance to be maintained in pathogen populations after antibiotics have been withdrawn from use. Resistance mutations vary in their potential for compensatory adaptation, but the causes of this variation remain unknown. In this project, we will determine how the molecular mechanisms of antibiotic resistance and the (i) ecological and (ii) genetic context in which resistance evolves interact to determine (a) the fitness costs associated with antibiotic resistance and (b) the potential and mechanisms for adaptation to the cost of resistance. Conceptually, we will approach this problem using an interdisciplinary approach that combines theory from population genetics and systems biology into the same evolutionary framework. To carry out this research program, we will use high-throughput experimental evolution of resistance to the broad-spectrum antibiotic rifampicin in bacteria from the genus Pseudomonas. This research approach will allow us to measure both the costs of resistance and the (i) rate and (ii) mechanisms of compensation for this cost at an unprecedented scale. The results of this research program will provide key insights into the underlying drivers of resistance emergence and persistence, and it may ultimately be possible to apply the insights from this research program to help combat resistance in pathogen populations. At a more conceptual level, this research will provide an important experimental test of the roles of chance, necessity, and historical contingency in shaping the rate and mechanisms of adaptation."

Campo scientifico

Meccanismo di finanziamento

ERC-SG - ERC Starting Grant

Coordinatore

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

Indirizzo

Wellington square university offices
OX1 2JD Oxford
Regno Unito

Regione

South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire

Tipo di attività

Higher or Secondary Education Establishments

Contatto amministrativo

Gill Wells (Ms.)

Ricercatore principale

Roderick Craig Maclean (Dr.)

Collegamenti

Contatta l’organizzazione Sito web

Contributo UE

€ 1 196 639,00

Beneficiari (1)