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Metal pollution and antimicrobial resistance

Principal Supervisor: Dr Julie Morrissey - Department of Genetics

Co-supervisor: Professor Peter Andrew, Dr Kevin Waldron

PhD project title: Metal pollution and antimicrobial resistance

University of Registration: University of Leicester

Project outline:

Antibiotic resistant infections are a significant clinical and economic burden globally. The discovery of new antibiotics has decreased worryingly over the past twenty years with very few antimicrobial drugs being introduced since the 1960s and resistance is now emerging to these last line antibiotics. Therefore there may soon be a time when there are infectious bacteria that cannot be treated with any current antibiotics. This will have a serious impact on all aspects of human and veterinary medicine.

Copper is an essential but toxic metal in high concentrations. Copper toxicity is exploited clinically as an antimicrobial therapy, as well as in the agrochemical and meat-production industries. Pollution of many different ecosystems has led to a significant increase in copper-resistant bacteria. Additionally, copper resistance genes are often genetically linked with antibiotic resistance genes. Together, this poses a considerable threat to human, animal and crop health because copper is critical for innate immunity and plant defence systems, and novel antibiotic resistant pathogens are emerging. Therefore the spread of bacterial copper resistance is of great concern.

The aim of this project is to understand the molecular mechanisms of copper and antimicrobial resistance.

We will use several interdisciplinary state of the art approaches in microbiology, genetics, biochemistry, infection biology and metalloproteomics to investigate the mechanisms of copper resistance and toxicity in the human and animal pathogen Staphylococcus aureus, and/or the human pathogen Streptococcus pneumoniae.

S. aureus is a significant problem for public healthcare, veterinary medicine and the food industry. S. pneumoniae is the major global cause of pneumonia. Both have high incidences of antibiotic resistance and so treating these bacteria in the future could be huge a problem. Additionally these bacteria can act as models for further investigations of plant pathogens.

Therefore this project will aim to develop future therapeutics against human, animal and plant pathogens. Therefore the objectives of this project are: 

  1. To determine the cellular mechanisms used to counteract copper toxicity.
  2. To investigate the links between copper and antibiotic resistance.
  3. To understand the role of copper resistance during infection.

References:

  1. Baker et al., 2011, ‘The Staphylococcus aureus CsoR regulates both chromosomal and plasmid-encoded copper resistance mechanisms,’ Environ. Microbiol. 13:2495-2507.
  2. Shafeeq et al., 2011, ‘The cop operon is required for copper homeostasis and contributes to virulence in Streptococcus pneumoniae,’ Mol Microbiol 81:1255-1270.
  3. Corbett D, Schuler S, Glenn S, Andrew PW, Cavet JS, Roberts IS. The combined actions of the copper-responsive repressor CsoR and copper-metallochaperone CopZ modulate CopA-mediated copper efflux in the intracellular pathogen Listeria monocytogenes. Mol Microbiol. 2011 Jul;81(2):457-72
  4. Tottey et al., 2012, ‘Cyanobacterial metallochaperone inhibits deleterious side reactions of copper,’ Proc Natl Acad Sci USA 109:95-100.

BBSRC Strategic Research Priority: Molecules, cells and systems

Techniques that will be undertaken during the project:

  • Microbiological techniques
  • RNA and DNA analysis
  • Bioinformatics
  • Metalloproteomics

Contact: Dr Julie Morrissey, University of Leicester