Small-Molecule G-Quadruplex (G4) Ligands as Candidate Antibacterials for Resistant Bacteria

Project Code

MRCIIAR25Br Spencer 

Research Theme

Infection, Immunity, Antimicrobial Resistance and Repair

Project Summary Download

Summary

Increasing resistance makes developing new antibiotics, that kill bacteria by different mechanisms from existing agents, a public health priority. G-quadruplexes (G4s) are specific nucleotide structures, formed by guanine-rich sequences, that represent potential antibacterial targets as their stabilisation by small-molecules disrupts cellular processes (DNA replication, transcription). We have identified several small molecules with antibacterial activity that bind G-quadruplex sequences in vitro. This project combines imaging, whole-genome sequencing and proteomics, together with antibacterial susceptibility assays and investigations of resistant mutants; to investigate their cellular targets and killing mechanisms and assess the potential of G4 ligands for development of new generations of antibiotics.

Lead Supervisor

Professor James Spencer

Lead Supervisor Email

Jim.Spencer@bristol.ac.uk

University Affiliation

Bristol