Antibiotic Tolerance: Prevalence, Molecular Basis and Consequences

Tuesday 23 May 2023

MMB Hybrid Seminar by Dr Jo Hobbs, University of St Andrews

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Tuesday 23 May 2023, 12:00 - 13:00
Discovery Centre

University of Dundee
Old Hawkhill

Discovery Centre
Booking required?

Host: Professor Nicola Stanley-Wall

Location: Discovery Centre, Sir Kenneth & Lady Noreen Murray Seminar Room, 2.84


Antibiotic tolerance describes the ability of a bacterial population to survive transient exposure to an otherwise lethal concentration of antibiotic without exhibiting resistance. Tolerance is not detected by routine susceptibility testing, so we know very little about its clinical prevalence and significance. However, there is evidence to suggest that it contributes to persistent infections, is associated with higher mortality rates and, potentially, acts as a precursor to resistance. The phenomenon of tolerance has been detected in a variety of pathogenic bacteria and most extensively studied in Staphylococcus aureus. In this seminar, I will present my research to date on the prevalence, molecular basis and consequences of antibiotic tolerance in S. aureus. We have developed a simple biochemical diagnostic test that can detect tolerance among clinical isolates of S. aureus, and we are in the process of using this test to screen libraries of clinical isolates from persistent infections. We have also discovered that the stringent response represents a clinically important mechanism of tolerance in S. aureus. Mutations in the stringent response controller, Rel, confer multidrug tolerance as a result of reduced growth and elevated (p)ppGpp, the signalling molecule of the stringent response. Other mechanisms of tolerance are under investigation but appear to affect other signalling pathways that are intrinsically linked to the stringent response. Finally, we have found that the partial stringent response activation induced by clinical Rel mutations promotes the conjugal transfer of multiresistance plasmids. Therefore, tolerance-conferring mutations represent a risk to our ability to effectively treat bacterial infections on multiple fronts.




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Event type Seminar
Event category Research