GENETIC INSTABILITY OF THE GLOBAL REGULATOR AGR EXPLAINS THE PHENOTYPE OF THE XPR MUTATION IN STAPHYLOCOCCUS-AUREUS KSI9051

Staphylococcus aureus KSI9051 has a complex mutation that was associat ed with the aberrant expression of cell surface and extracellular prot eins (M. S. Smeltzer, M. E. Hart, and J. J. Iandolo, J. Bacteriol. 61: 919-925, 1993), This mutation was named xpr, although no specific gene was identified. Here this mutation is referred to as Delta 1058::Tn55 1. In this study, we show that in strain KSI9051, the Delta 1058::Tn55 1 mutation occurred coincidentally with a frameshift in agrC that iis expected to truncate the sensor component of the known staphylococcal global regulatory locus agr, Remarkably, pleiotropic mutations affecti ng cell surface and extracellular proteins are generated at frequencie s approaching 50% upon the transduction of erythromycin resistance (Em (r)) encoded by Delta 1058::Tn551 from S. aureus KSI905 back to its pa rental strain, S6C, Three independent isolates created in the manner o f KSI9051 contained mutations within agrC. Each isolate had different mutations, suggesting that the transduction of Em(r) encoded by Delta 1058::Tn551 affects the stability of agrC in S6C, In similar experimen ts with strains from an S. aureus 8325 genetic background, a mutant Ag rC phenotype could not be isolated, implying that strain S6 has aberra nt genetic behavior. A comparison of the nucleotide sequences of AgrC from several strains revealed seven errors in the GenBank entry for ag r (X52543); these data were confirmed with plasmid pRN6650, the origin al wild-type clone of agr.