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Role of the stringent response to promote biocide induced antibiotic tolerance in Staphylococcus aureus biofilms.

   School of Life Sciences

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  Dr K Hardie  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

The selection of antibiotic tolerant bacteria is of emerging concern and is thought to contribute to treatment failure. Our preliminary data supports the hypothesis that widely used biocides can promote such tolerance in the major human pathogen Staphylococcus aureus by activation of the stringent response. This was also observed in biofilm grown bacteria. The stringent response regulated phenol soluble modulins (PSMs) are likely involved in biocide induced biofilm composition. The studentship will build on our previous cooperation and benefit from complementary global gene expression data, methods and expertise. Transcriptome and metabolome data will be generated to decipher the molecular mechanisms triggered by biocide induced stringent response and biofilm alterations. This will inform future treatment options. In Tubingen, the student will define underlying molecular pathways by construction and global analyses of a defined set of engineered strains. In Nottingham, the student will analyse biofilms with a special focus on the role of PSMs in polymicrobial biofilms and antibiotic tolerance. Working across disciplines, the student will undertake cross-correlative imaging to map gene expression, microbial metabolism, and biofilm architecture with PSM production and biocide exposure. Including our novel oxygen-sensitive nanosensors within biofilms will enable parallel dynamic monitoring of reactive oxygen species.

The two universities provide first class facilities and learning environments supported by expertise and dedicated researchers. The collaboration enables the Tubingen tools (mutants) to be analysed on UoN imaging platforms using their range of biofilm models.

The supervisors have vibrant research groups hosted in state-of-the-art laboratories. Kim Hardie has an extensive track record in molecular microbiology of pathogenicity and leads the pathogen imaging facility within the Cross-disciplinary Biodiscovery Institute. Jon Aylott has developed optical nanosensors for sensitive real time monitoring of pH and oxygen. Jon and Kim collaborate to map the environmental microniches of biofilms, and are co-Investigators of the National Biofilm Innovation Centre (NBIC). At the University of Tübingen, Christiane Wolz is a leading expert in the study of the stringent response, and has an broad selection of defined mutants supported by expertise in molecular engineering. Hannes Link leads a metabolomics pipeline that generates population measurements to complement the 2D and 3D mapping of metabolites using a range of analytical tools housed within the flagship nmRC facility at the University of Nottingham.

The training opportunities include cutting-edge fluorescent microscopy, transcriptomics, optical nanosensor utilization, LC-MS metabolomics, cryo-EM, cryo-orbiSIMS, and molecular microbiology. In addition both Universities offer a host of practical training courses, there is an active research seminar programme and wellbeing support.

How to apply:   

Please send CV and cover letter to Edward Gordon ([Email Address Removed]). 

Application Deadline: 30th May 2022

Funding Notes

3 years duration (July 1st 2022-August 31st 2025); FT; Funded by Tübingen-Nottingham Joint University Research Initiative to cover student stipend of £15,609 rising with inflation annually plus research consumables, travel and training. Tuition fees for home, EU and international students. The studentship will be primarily based in the UK at the University of Nottingham, with up to 12 months in Germany (University of Tübingen).

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