Metal Homeostasis in Staphylococcus aureus and Listeria monocytogenes

Bacteria have evolved mechanisms which enable the intracellular control of metal concentrations and, interestingly, these systems play important roles in virulence. There has been a global emergence of Staphylococcus aureus strains, called community-acquired methicillin resistant S. aureus (CA-MRSA), which can infect healthy humans who have had no previous exposure to healthcare situations. USA300 is a CA-MRSA strain which rapidly spread across the United States. Previous studies have suggested that a horizontally transferred copper resistance locus (copXL), which encodes a copper transporter (CopX) and lipoprotein of unknown function (CopL), may explain the success of USA300. The USA300 copper response has not been investigated, therefore this project focused on understanding how copXL acquisition, affects the USA300 response to copper. In this study, copper was shown for the first time to trigger a shift to anaerobic respiration in USA300, affecting the TCA cycle and fermentation pathways. Additionally, copper was shown to enhance the ability of USA300 to invade host cells and CopL may play an important role as an adhesin. This could have implications in healthcare settings, where the use of copper surfaces and copper coated medical devices are increasingly being considered for the reduction of healthcare-associated bacterial infections.

Investigation of S. aureus CopL in other bacteria led to the identification of CopL homologues encoded on plasmids in Listeria monocytogenes. Interestingly, these plasmids were found in many L. monocytogenes strains and also encoded other predicted metal resistance genes. The importance of these plasmids in L. monocytogenes has not been explored. This work showed that plasmids encoding multiple predicted metal resistance genes in L. monocytogenes confer resistance to copper and cadmium. Additionally, these plasmids were highly associated with strains isolated from foods, particularly meats, providing the first evidence of a possible connection between L. monocytogenes colonisation/survival on meats and harbourage of metal resistance genes.