"Bacterial antimicrobial resistance has become one of the major concerns in modern medicine. It is currently responsible in Europe for 15 times as many deaths as AIDS every year. Not surprisingly this phenomenon is one of the Top Six Health Topics for the eCDC.
Bacteria have shown a remarkable evolvability towards resistance. One of the most worrisome mechanisms observed, is the integron, a highly efficient gene-recruitment platform. In addition to rising resistance, there are no encouraging perspectives in the drug discovery field. Thus, containment is the major asset in combating resistance. Nevertheless new and creative approaches are being assessed. A good example is the study of molecules against the integrase. A deep knowledge on the integrase’s activity and its regulation is at the basis of any major achievements in the field.
This project aims to better understand integrons and to acquire new knowledge that will ultimately help combat antimicrobial resistance. The first set of experiments will unravel the behaviour of integrons in vivo. By developing a mouse model, we will study the influence of antibiotic therapy in the integrase induction through SOS response in the gut. Further work will be focused on the in vivo integron/plasmid synergy, as single stranded DNA transmission during conjugation can trigger integrase activation in vitro through SOS response. Such interaction is especially worrisome as many resistance plasmids carry resistance integrons.This data will help understand the behaviour of integrons and the dynamics of integrases in their natural environment.
Altogether, the results of this project will mean a breakthrough in understanding the evolutionary potential integrons confer to bacteria. This knowledge will definitely help develop efficient tools to fight antimicrobial resistance."
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