Staphylococcus aureus is a pathogenic bacterium that causes a wide spectrum of human diseases and is a leading cause of nosocomial infection in the UK. Metal homeostasis is an important aspect of bacterial biology as transition metals such as copper and iron are required as enzyme cofactors but can also be toxic to cells at high concentrations. These metal homeostasis systems can be important for virulence. However, several important aspects of S. aureus metal homeostasis remain to be defined. This project focuses on novel S. aureus iron/Fur gene regulation and copper homeostasis. Fur is a well-described DNA binding repressor protein, found in many pathogenic bacteria. In S. aureus, Fur has been seen to both activate and repress genes in iron replete and iron restrictive conditions, and there is also Fur independent iron regulation. However, the regulatory mechanisms involved remain undefined. This investigation into novel iron regulation identified a new S. aureus iron regulator, LysR. lysR expression was found to be auto-regulated and activated by Fur in low iron. Phenotypic analysis suggested a possible role for LysR in the control of genes of the histidine utilisation pathway, as well as oxidative stress resistance. Two copper responsive operons have been found in S. aureus; copAZ and copB/mco. However, many important aspects of the S. aureus response to copper remain undefined. In this study, copper tolerance was shown to vary between strains and ATCC 12600 was identified as the first hyper copper-tolerant S. aureus, due to a transferable copper-resistance plasmid. A new S. aureus regulator, CsoR, was found to control the copper response of copAZ and both chromosomal and plasmid encoded copB/mco. Finally, this data shows that H2O2 scavenging is an essential S. aureus copper resistance mechanism and that extracellular surface copper toxicity is important in S. aureus.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:551867 |
| Date | January 2009 |
| Creators | Baker, Jonathan Peter |
| Contributors | Morrissey, Julie |
| Publisher | University of Leicester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/2381/9923 |
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