Antibiotics frequently fail to clear infections even when the bacterial pathogen is not resistant. One of the causes of this treatment failure is the ability of a subpopulation of bacteria to transiently enter a non-growing ‘persister’ state in which they can survive antibiotics and revive after treatment ends leading to infection recurrence. Because tolerant or persistent strains are not resistant they are cannot be identified by traditional susceptibility testing methods used in clinical settings (which measure the antibiotic minimum inhibitory concentration, MIC). Furthermore, antibiotic tolerance-conferring mutations can rapidly evolve in response to treatment. The true rates of antibiotic tolerance are therefore very poorly understood. In many cases these bacteria are multidrug-tolerant and there is a clear need to develop new approaches to target these hard-to-treat bacterial populations.
Focusing in particular on Escherichia coli, the Stracy lab are working to understand the physiology of these ‘sleeping’ bacteria in order to develop new way to eradicate them, thereby helping to stop infections recurring and reduce the number of antibiotic courses that patients need to take. To achieve this, we take and interdisciplinary approach using a variety of techniques including microbiology methods, genetics, genomics, single-cell and single-molecule microscopy methods. This project will involve using lab evolution to generate high-tolerance mutant E. coli strains and identify causative mutation with whole genome sequencing. Together with an existing collection of tolerant E. coli mutants and collections of clinical isolates, these evolved strains will be characterized with high-throughput and cell killing assays and microscopy methods. We will then assess the efficacy classical antibiotics and novel potential therapeutics in killing tolerant strains or inhibiting the evolution of tolerance during antibiotic treatment.
Stracy lab
Studying how bacteria respond to antibiotics from multiple perspectives; ranging from molecular biology to infection epidemiology
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