Abstract
Antimicrobial resistance is one of the biggest public health threats. Vancomycin resistant enterococci (VRE), causing e.g. urinary tract and bloodstream infections, are a prime example. Treatment options for VRE are limited, requiring the use of last-resort antibiotics such as linezolid. Hence, the emergence of linezolid resistant VRE (LVRE) poses a major health risk. Fortunately, the prevalence of linezolid resistant enterococci (LRE) is low and even lower among VRE. Worryingly, LRE are also found in animals, highlighting the need for a One Health approach. The extremely low prevalence of LVRE raises the question whether this is a mere coincidence, with the prevalence still able to rise in the future, or if it will always be limited. This project aims to elucidate the emergence and spread of LVRE by integrating state-of-the-art genomic analysis with wet-lab phenotypic assessments using a One Health approach. It seeks to characterize the population structure and relatedness between human and veterinary VRE, LRE and LVRE using whole genome sequencing, metadata and phylogenetic analysis. Furthermore, it will delve deeper into microbiological dynamics and study the risks of VRE evolving into LVRE through the acquisition of resistance conferring mutations or mobile resistance genes by using adaptive laboratory evolution, conjugation-assays and competition-assays to investigate whether excessive fitness costs may be a contributing factor hindering the emergence and spread of LVRE.
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