1887

Abstract

Copper is an essential metal in both eukaryotes and prokaryotes, however excess levels are toxic. Bacteria have developed mechanisms, such as efflux and sequestration, to counteract these toxic effects. Significantly, copper has been shown to be important in host innate immunity as an antibacterial mechanism against invading pathogens, via active transport of copper into the phagosome. Worryingly, there has been a global emergence of S. aureus strains with increased antibiotic resistance (e.g community-acquired methicillin resistant S. aureus (CA-MRSA)), which unlike typical S. aureus, can infect healthy humans with no previous exposure to healthcare situations. These isolates show increased resistance to innate immunity and reduced clearance from healthy airways compared to other clinical isolates. Recently, we identified a novel horizontally transferred copper resistance locus, copXL, in CA-MRSA which is in addition to the core copper homeostasis operon (copAZ) found in all S. aureus and is not present in established S. aureus human lineages. copXencodes a copper efflux transporter and copLis predicted to encode a lipoprotein of unknown function. This operon confers resistance to extremely high concentrations of copper compared to other S. aureus and, notably, is important for survival within intracellular macrophages. The recent evolution and success of USA300 may be due to possession of these additional copper resistance genes, enhancing bacterial fitness through increased resistance to copper-dependent bactericidal innate immunity. The function of CopL in S. aureus macrophage survival and copper hyper-resistance is currently being investigated to combat this highly effective copper resistance mechanism and spread of these highly virulent pathogens.

Loading

Article metrics loading...

/content/journal/acmi/10.1099/acmi.ac2019.po0046
2019-04-08
2019-10-15
Loading full text...

Full text loading...

http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.ac2019.po0046
Loading
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error