Staphylococcus aureus is a versatile pathogen, whose infections, due to the increasing emergence of antibiotic resistant strains, are causing considerable alarm within the medical community. The expression of many S. aureus virulence factors is under the control of the agr quorum sensing system. A model was proposed for the function of agr mediated quorum sensing in staphylococcal invasion of cells, which suggested that arg related products were necessary for escape from the endosome and subsequent release and growth in the cytoplasm. It was proposed that in an extracellular environment, agr was down-regulated due to dilution of the agr peptide in the surrounding fluids. Upon uptake, the agr peptide concentrations increased rapidly when the bacteria were confined within the endosome, and that lysis occurred due to the induction of agr related exoproteins. Our previous studies with S. aureus RN6390 support the hypothesis that agr expression precedes host endosomal lysis. Recent studies have shown that S. aureus strains derived from the NCTC 8335 lineage, (e.g. RN6390, 8325-4) carry a deletion in rsbU. As rsbU encodes a positive regulator for the activation of the stress response sigma factor SigB, the deletion results in cells that are phenotypically sigB defective. If internalisation induces a stress response in S. aureus, the defect in rsbU is expected to affect the level of agr expression and change the internalisation capabilities of the organism. A recent study indicates that differences in the regulation of sarA and agr exist within different strains of S. aureus, but it is uncertain if this would affect virulence. As our previous experiments were performed with S. aureus RN6390, the data may be at variance with that obtained with 'wild type' S. aureus. This study investigates the possible similarities or differences of S. aureus rsbU~+ and rsbU~- strains using a novel GFP-Lux dual reporter system and high throughput microtitre plate assay.
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