Opis projektu
Genetyka pomoże w rozpoznaniu pięty achillesowej bakterii
Antybiotykooporność stanowi poważne zagrożenie dla zdrowia, które obniża skuteczność operacji i leczenia chorób. Istnieje pilna potrzeba zrozumienia czynników wywołujących antybiotykooporność i opracowania sposobów jej przeciwdziałania. Prace zespołu finansowanego przez UE projektu uCARE opierać się będą na hipotezie, że bakterie wykorzystują podobne mechanizmy antybiotykooporności i lekooporności, które atakują ludzkie cząsteczki. Aby wyjaśnić powszechne mechanizmy i sieci związane z opornością, naukowcy wykorzystają techniki genetyki chemicznej i ewolucji eksperymentalnej. Opisanie rozwoju lekooporności pomoże w zmianie obecnych polityk lekowych.
Cel
The evolution and spread of antibiotic resistance has become a public health concern of the utmost severity, making once treatable diseases deadly again and undermining our living standards. New therapies are imperative, but equally important are the understanding of the full repertoire of drivers of antibiotic resistance and the identification of ways to counteract them. We have recently established that ~250 non-antibiotic drugs have direct, strong and often broad antibacterial effects on human gut microbes. Moreover, preliminary data indicate that bacteria use similar general resistance mechanisms against both drugs with human targets and antibiotics. This implies that polypharmacy may be a hitherto unnoticed driver of antibiotic resistance. We will use chemical genetics and experimental evolution to systematically map the cross-resistance between human-targeted drugs and antibiotics, and elucidate underlying resistance mechanisms. Using these data, we will next seek to identify antidotes for the antimicrobial side-effects of non-antibiotic drugs, and exploit human-targeted drugs for reverting existing antibiotic resistance. At the genetic level, we will use high-throughput reverse genetics to expose the Achilles heels of bacterial cellular networks for resistance development. Finally, we will uncover the antimicrobial mode of action of tens of human-targeted drugs using thermal proteome profiling and chemical genetics. Together with the genetic information, this line of research will yield design principles and possibly new drug candidates for longer-lived, resistance-proof drug combinations. Overall, this project aims at improving our fundamental biological understanding of antibiotic resistance and the paths to prevent, delay or revert it. It can also set the basis for revisiting current medication policies. The derived principles are likely to be relevant to other diseases and therapies, in which resistance development is an issue.
Dziedzina nauki
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- natural sciencesbiological sciencesgenetics
- medical and health scienceshealth sciencespublic health
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Słowa kluczowe
Program(-y)
Temat(-y)
System finansowania
ERC-COG - Consolidator GrantInstytucja przyjmująca
69117 Heidelberg
Niemcy