Alkaline pH decreases expression of the accessory gene regulator (agr) in Staphylococcus aureus

The effect of alkaline pH on expression of the accessory gene regulator (agr) in Staphylococcus aureus was examined. agr, a global regulator, affects the expression of numerous exoproteins, including alpha-hemolysin, toxic shock syndrome toxin 1, protein A, and staphylococcal enterotoxins types B, C, and D. agr contains two major, divergent transcripts, designated RNAII and RNAIII. In this study, the level of RNAIII was used to monitor agr expression because this transcript and/or its protein product(s) appears to be responsible for altering target gene expression. S. aureus FRI1230 and its Agr- derivative were examined in a fermentor system which allowed batch cultures to be maintained at a constant pH. FRI1230 cultures were grown at pH 6.5, 7.0, 7.5, and 8.0. Northern (RNA blot) analysis of samples revealed that maximal agr expression occurred at pH 7.0, with virtually no RNAIII observed at pH 8.0. The effect of alkaline pH on an agr target gene, sec, was also evaluated. sec expression was reduced at alkaline pH in strain FRI1230 (Agr+) but not in its Agr- derivative, indicating that an intact agr allele is required for the pH effect on sec. Examination of batch cultures under conditions of nonmaintained pH gave results that were also consistent with a role for alkaline pH in repressing agr expression.