Agnes Mihalyi was awarded a BSc and MSc in Chemical Engineering at the Technical University of Budapest (currently named Budapest University of Technology and Economics). She started a PhD under the supervision of Timothy D.H. Bugg in 2010.

Research

Screening for novel inhibitors for the enzyme MraY, involved in bacterial cell wall peptidoglycan biosynthesis

The biosynthetic pathway of the bacterial peptidoglycan is an important target for the development of novel antibacterial agents. Bacterial drug resistance is an increasingly serious problem that threatens public health, and researchers need to develop new drugs. This research focuses on the first two lipid-linked steps of peptidoglycan biosynthesis. The two enzymes required for these steps are MraY and MurG. A fluorescence MraY assay was developed to test known and potential MraY inhibitors such as nucleoside natural products produced by various Streptomyces strains and their synthetic analogues, tryptophan and arginine-rich antimicrobial peptides and small molecule analogues of E-protein. A high-throughput fluorescence MraY assay was also developed in microtitre plate format and around 2,000 compounds were screened from the Diversity Set of the National Cancer Institute against MraY, in order to identify novel inhibitors. In addition, radiochemical MraY and MurG assays were developed for compounds that interfere with fluorescence. These fluorescence and radiochemical assays proved to be suitable for detecting inhibition in Streptomyces culture supernatants and cell extracts. Agnes is currently investigating the hits from the Diversity
Set of the National Cancer Institute and from the Streptomyces cell extracts.