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To investigate antibiotic-induced stress responses in Staphylococcus aureus

  • Full or part time
  • Application Deadline
    Saturday, August 31, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

About This PhD Project

Project Description

Bacterial pathogens, including those commonly associated with healthcare-related infection (HAI), such as Staphylococcus aureus, can acquire resistance to antibiotics. There are instances however, when the organisms causing an infection appear fully susceptible to the prescribed drug yet treatment fails. Unlike antibiotic resistance that signifies the inherited ability of the organism to grow in the presence of the antimicrobial, persistence to an agent occurs through phenotypic changes leading to antibiotic tolerance and ultimately failure to resolve the infection.

S. aureus has developed a plethora of cellular stress response mechanisms that allow it to detect, respond and survive external stresses: including oxidative, osmotic and cold stress; DNA damage, nutrient starvation and exposure to antimicrobial compounds. When S. aureus are challenged with antimicrobials the cells undergo physiological changes in which there is an overall switch from the expression of genes required for growth to those that will aid survival. For example, the physiological response referred to as the ’stringent response’ (SR), has been linked with exposure to certain antibiotics. The SR is characterised by the accumulation of alarmones, ppGpp and pppGpp, which are usually controlled by the synthase RelA and hydrolase SpoT. Current research suggests that RelA is responsible for both functions in S. aureus. It is believed that the accumulation of these small intracellular signalling molecules leads to the continuous activation of the SR. This response has been linked to altered expression of virulence factors, biofilm formation, and development of antibiotic tolerance and persistence of infection. It remains unclear whether the recalcitrance to antibiotic therapy associated with a stress response is a direct effect of the antibiotic or indirect through a cascade of events leading to the effect.

In previous studies we have demonstrated induction of changes in S. aureus by oxazolidinone antibiotics and related this with virulence gene modulation and an upsurge in pathogenicity. It remains unclear if this stress-response is specific only to certain agents or if the effect is typical of exposure to antibacterials. In addition, bacterial cells which are growing attached to a surface in the form of a biofilm, which is fundamental to many infections, are metabolically different from planktonic counterparts, therefore responses to stress may differ with the growth modality of the cells. At present any differences remain unclear.

The aim of this proposed study is to investigate antibiotic-induced stress-responses in the pathogen Staphylococcus aureus that can alter bacterial virulence and are potentially associated with treatment failure.
The successful candidate will gain experience in a range of microbiology, molecular biology and imaging techniques to address this aim. The student will join an experienced research team with clinical and industrial links to work on a project that has a real potential to inform patient treatment.

Informal inquiries can be made to Dr Sue Lang () and details of the application process, including the application form, are available from the Leeds Beckett University Graduate School:
https://www.leedsbeckett.ac.uk/the-graduate-school/research-degrees-at-leeds-beckett/studentships/clinical-and-applied-sciences-studentships/

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