Hector Fellow

UNRAVELLING THE ENVIRONMENTAL LANDSCAPE OF BACTERIAL REVIVAL AFTER ANTIBIOTIC TREATMENT

01/11/2021 to 30/09/2024

Resistance of bacterial pathogens to antibiotics is a serious threat to global health, with a predicted death toll of 2.4 billion people worldwide in the next 30 years, and costs up to $US3.5 billion per year. New solutions to fight resistance are imperative, both to rescue old antibiotics and to undermine resistance to newly discovered ones. Antibiotic tolerance – a transient physiological state where bacteria tolerate antibiotics without being resistant – is widespread in bacteria, including Salmonella enterica and Mycobacterium tuberculosis, and leads to relapsing infections. While much attention is given to the mechanisms driving tolerance, not much is known about the revival of these bacteria. Which environmental conditions favour their revival, potentially relapsing the infection? The aim of this project is to elucidate environmental cues and molecular mechanisms of revival of the pathogen Salmonella Typhimurium after antibiotic treatment. I propose to do so by applying high-throughput approaches to assess bacterial revival post antibiotic treatment in large compound libraries (>2000 compounds), combined with genetic screening of a knockout mutant collection for selected cases for gaining mechanistic insight. The most interesting results will be validated during Salmonella infection of macrophages (cell-culture), where tolerance has been recently linked to the spread of antibiotic resistance.