Principal Investigator (PI)
The Foundation is providing £206,210 in support.
Edna Ondari - Connor Edwards Bytom
This project will benefit tremendously from GSK’s extensive HTS capabilities and expertise, in particular with respect to intra-macrophage assays as well as persister experience in the fields of TB and Chagas, and also from access to its compound collection.
Non-growing persister bacteria are antibiotic tolerant and contribute to treatment failure and acquisition of antibiotic resistance in multiple infection contexts, including invasive non-typhoidal Salmonellosis (iNTS). iNTS kills approximately 50,000 people per year in sub-Saharan Africa, disproportionately affecting children. Despite this, persister biology remains poorly understood, and most drug discovery screening platforms seek compounds that inhibit growth without assessing impacts on non-growing persisters.
This project will develop a novel screening cascade that focuses on compounds capable of killing the persisters that survive conventional antibiotics. As a proof of concept, we will screen key sets of compounds and deploy a series of secondary screens on a subset of identified hits. This will allow us both to optimise the cascade and identify compounds for further development. Additionally, we will develop persister-specific assays to use as secondary screens, leading to new insights in persister biology with potentially broad applications to other infectious diseases.