Antibiotic resistance represents a rapidly growing global health problem caused by the use and misuse of antibiotics and spread of resistant bacteria as well as the lack of industrial development of new antibiotics. The urgency of the resistance problem makes the development of experimental and theoretical tools and methods to understand and predict (and by inference prevent) the development of antibiotic resistance a high priority. This project aims to describe and predict the dynamics of antibiotic resistance development at the level of the drug target, the microbe and the host.. The obtained results will have general biological implications with regard to molecular evolution and bacterial adaptation, virulence and transmission. Most importantly, our results will generate strategies to reduce the rate of resistance of development
The intensive use and misuse of antibiotics have resulted in antibiotic resistance among many human pathogens and there is a growing concern that the loss of therapeutic options will present us with a post-antibiotic era where present and future medical advances are negated. Resistant bacteria dramatically reduce the possibilities of treating infections effectively and increase the risk of complications and fatal outcome for patients with severe infections. Thus, antibiotic resistance represents a major public health concern and economic problem both within EU and globally.[+] Read More
The main aim of this proposal is to describe and predict the dynamics of antibiotic resistance (AR) development at the level of the drug target, the microbe and the host. At the present time, we do not know how to reduce or reverse the development of resistance, since current knowledge about the mechanisms and evolutionary constraints that drive the emergence and survival of resistant strains is scarce. In addition, the severe lack of knowledge means that we do not know how the various parts of the puzzle fit together, i.e. how do we connect antibiotic use patterns --> bacterial resistance mechanisms --> bacterial physiology and fitness --> bacterial survival within a host --> bacterial spread between hosts. This proposal aims at generating the knowledge needed to answer this question by developing novel conceptual and experimental approaches. In addition, we intend to explore several approaches both with regard to new principles for rationally choosing drug targets and drugs with minimized risk of resistance development.
The obtained results will have general biological implications with regard to molecular evolution and bacterial adaptation, virulence and transmission. Most importantly, our results will have several medically relevant applications. The expected achievements of our objectives are to: