Staphylococcus aureus is a human pathogen responsible for a significant amount of disease and morbidity worldwide. When this bacterium invades a human host it encounters a number of different stresses, such as nutrient limitation. The bacteria respond to these stresses by switching on a response called the stringent response. This response results in the synthesis of two small nucleotides, collectively referred to as (p)ppGpp. These nucleotides are the effectors of the stringent response and function by binding to target proteins leading to the bacterial cells shutting down active growth and entering a slow growing or persistent state that promotes survival and leads to chronic infections. In S. aureus (p)ppGpp is synthesised by the bifunctional enzyme RSH and the monofunctional enzymes RelP and RelQ, however relatively little is known about the production and regulation of these synthases. This project will use molecular genetics to provide an in-depth characterisation of the environmental host signals that trigger production of these enzymes on both a transcriptional and translational level. Additionally this project will make use of an S. aureus mutant library to identify which regulator(s) control the transcription of these genes on a molecular level. Altogether this project will provide key insights into the synthesis of (p)ppGpp by these enzymes and so generate important mechanistic data on the pathogenesis of S. aureus. |
The Team
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