Title:	Molecular evolution of antibiotic resistance
DNr:	SNIC 2021/6-309
Project Type:	SNIC Medium Storage
Principal Investigator:	Yasmin Binti Shamsudin <yasmin.shamsudin@kemi.uu.se>
Affiliation:	Uppsala universitet
Duration:	2021-11-30 – 2022-12-01
Classification:	10203 10407 10603
Keywords:

Abstract

Antibiotic resistance is one of the most dangerous developments for global health. The consequence of antibiotic resistance is that fewer of the traditional antibiotics are useful for treating bacterial infections, resulting in longer recovery times and more deaths among the young, elderly, and people with weakened immune systems, such as post-operational and intensive care unit patients. As bacteria are rapidly becoming resistant to available antibiotics, new ones are urgently needed to replace them. Indeed, the challenge of developing new drugs is evident in the slow progression of novel antibiotics to the market. Thus, alternative solutions are needed. Bacteria produce and release lactamase enzymes that hydrolyze beta-lactam antibiotics, such as penicillins, cephalosporins, cephamycins, and some carbapenems, efficiently breaking them down and establishing multi-resistance. If these enzymes could be inhibited, current antibiotics could still be used. Such a solution will save lives without the need for entirely new classes of antibiotics. However, as beta-lactamases have gradually evolved to optimize the inhibition of antibiotics, these enzymes could evolve further to counter their own inhibition. In this project we strive to understand the process of beta-lactamase evolution through computational modelling and simulations, leading to the design of new co-antibiotics that can be used in the longer term.