The human immune system uses antimicrobial metals as part of its defence mechanism. Excess copper is highly toxic and accumulates at sites of infection and acting within macrophages to kill engulfed pathogens.
Our recent publication (Purves et al., 2018) showed that the highly virulent, epidemic, community acquired methicillin resistant Staphylococcus aureus, shows altered infectivity compared to typical S. aureus, has acquired an additional copper hyper-resistance mechanism that increases survival in 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 emerging highly pathogenic and antibiotic resistant isolates and other bacterial pathogens.
The aim of this project is to investigate the role of acquired metal resistance genes in increased infectivity and environmental persistence of Listeria monocytogenes, which is a major food borne pathogen, commonly found in food processing environments, that causes life threatening food poisioning.
Microbiological techniques, RNA and DNA analysis, transcriptomics, ex vivo and in vivo infection models.
self funded must have microbiology laboratory experience
Baker et al., 2011, ‘The Staphylococcus aureus CsoR regulates both chromosomal and plasmid-encoded copper resistance mechanisms,’ Environ. Microbiol. 13:2495-2507. Corbett D, Schuler S, Glenn S, Andrew PW, Cavet JS, Roberts IS. 2011 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. Jul;81(2):457-72 Purves et al. 2018 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. Environ Microbiol. 20(4):1576-1589. Zapotoczna et al. 2018. Mobile genetic element-encoded hypertolerance to copper protects Staphylococcus aureus from killing by host phagocytes. (2018) MBio. 9(5). pii: e00550-18.