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The role of copper resistance in Staphylococcus aureus infection


Department of Genetics and Genome Biology

Leicester United Kingdom Immunology Microbiology Molecular Biology

About the Project

Excess copper is highly toxic and forms part of the host innate immune system’s antibacterial arsenal, accumulating at sites of infection and acting within macrophages to kill engulfed pathogens.

All bacteria possess mechanisms to resist the toxicity of the essential micronutrient copper. However, our recent publications show that methicillin resistant Staphylococcus aureus (MRSA) have acquired additional copper hyper-resistance mechanisms (Purves et al., 2018, Zapotoczna, 2018) that increase survival during their interaction with human immune cells.

The highly virulent community acquired MRSA USA300 has acquired a novel copper resistance locus that is uniquely associated with the methicillin resistance element (Purves et al., 2018). This locus confers copper hyper-resistance and is required for S. aureus USA300 intracellular survival within macrophages. These genes are additional to existing core genome copper resistance mechanisms, and are not found in typical S. aureus lineages, but are increasingly identified in other emerging pathogenic isolates and other pathogenic bacteria.

Our current transcriptional data show that the presence of excess copper alters the expression of several metabolic pathways and virulence genes.

The aim of this project is to investigate the role of copper resistance mechanisms in the increased infectivity of CA-MRSA.

Objectives are to:

1. Establish the molecular mechanisms involved in the copper-responsive regulation of virulence factors.

2. Determine the importance of copper-regulated metabolic pathways in

(a) resistance to copper toxicity.

(b) survival against human innate immunity.

The student will be part of a lively and friendly interdisciplinary research group and will be trained in a wide range of molecular microbiology techniques including transcriptional analysis, proteomics, tissue culture, fluorescence and electron microscopy to investigate the impact of additional copper resistance mechanisms on host-pathogen interactions.

Entry requirements:

• Those who have a 1st or a 2.1 undergraduate degree in a relevant field are eligible.

• Evidence of quantitative training is required. For example, AS or A level Maths, IB Standard or Higher Maths, or university level maths/statistics course.

• Those who have a 2.2 and an additional Masters degree in a relevant field may be eligible.

• Those who have a 2.2 and at least three years post-graduate experience in a relevant field may be eligible.

• Those with degrees abroad (perhaps as well as postgraduate experience) may be eligible if their qualifications are deemed equivalent to any of the above

• University English language requirementsapply. https://le.ac.uk/study/research-degrees/entry-reqs/eng-lang-reqs/ielts-65

Application enquiries to


References

1. Purves J, Thomas J, Riboldi GP, Zapotoczna M, Tarrant E, Andrew PW, Londoño A, Planet PJ, Geoghegan JA, Waldron KJ, Morrissey JA. A horizontally gene transferred copper resistance locus confers hyper-resistance to antibacterial copper toxicity and enables survival of community acquired methicillin resistant Staphylococcus aureus USA300 in macrophages. (2018) Environ Microbiol. doi: 10.1111/1462-2920.14088.

2. Zapotoczna M., Pelicioli-Riboldi G., Moustafa AM, Dickson E., Narechania A., Morrissey J A., Planet PJ., Holden MTG., Waldron KJ., Geoghegan JA. Mobile genetic element-encoded hypertolerance to copper protects Staphylococcus aureus from killing by host phagocytes (2018) MBio. 2018 9(5). pii: e00550-18.

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