Targeting a bacterial protein interaction ‘hub’ in the search for a new class of antibiotics — ASN Events
  1. Schedule
  2. Session Twelve - Poster Session D including Happy Hour & Trade Display
  3. Targeting a bacterial protein interaction ‘hub’ in the search for a new class of antibiotics

Targeting a bacterial protein interaction ‘hub’ in the search for a new class of antibiotics (#415)

Robyn E Mansfield 1 , Allen TY Lo 1 , Nan Li 1 , Joel DA Tyndall 2 , Nicholas E Dixon 1
  1. University of Wollongong, Wollongong, NSW, Australia
  2. National School of Pharmacy, University of Otago, Dunedin, New Zealand

There is a pressing need for the rapid development of new antibiotics to combat bacterial drug resistance. In this project, our ultimate goal is to develop a new class of antibiotics, which disrupt multiple protein interactions in bacteria by targeting an interaction 'hub'. In particular, we are focusing on the C-terminal six residues of single-stranded DNA-binding protein (SSB). These six residues are highly conserved in bacteria, and form a motif that mediates critical interactions with up to 14 different proteins involved in DNA replication, recombination and repair. Importantly, this C-terminal SSB motif is not present in humans.

We are using a combination of structural biology and protein binding assays to examine the conservation of these interactions in various pathogenic species of bacteria, and to identify compounds that can inhibit multiple SSB-interactions across a range of species. The resulting new ‘class’ of antibacterial compounds, tailored to inhibit multiple essential protein-protein interactions simultaneously, is predicted to possess a uniquely high resilience to the development of antibiotic resistance through target mutagenesis.