The role of proton motive force in expression of the Staphylococcus aureus cid and lrg operons

The Staphylococcus aureus cidABC and lrgAB operons have been shown to play a key role in the regulation of murein hydrolase activity and cell death in a manner thought to be analogous to bacteriophage-encoded holins and anti-holins respectively. Because of these functions, it has been proposed that the regulation of these operons is tightly controlled and responsive to key metabolic signals. The current study revealed the presence of two overlapping regulatory pathways controlling cidABC and lrgAB expression, one dependent on acetic acid and the other dependent on proton motive force (PMF). The latter pathway was analysed using agents that affect various aspects of the PMF. Gramicidin and carbonyl cyanide m-chlorophenylhydrazone (CCCP), antimicrobial agents that dissipate the ΔpH and membrane potential (ΔΨ), both enhanced lrgAB expression. Restoration of the PMF by incubation of the bacteria in the presence of glucose restored lrgAB expression back to the uninduced state. In addition, valinomycin, which specifically collapses the ΔΨ, also induced lrgAB expression. In contrast, nigericin, which dissipates the ΔpH component of the PMF, was found to have a minimal effect on ΔΨ and lrgAB transcription. Finally, the ΔΨ-inducible expression of lrgAB was shown to be dependent on the previously characterized LytSR two-component regulatory system that is involved in the regulation of autolysis. The results of this study support a model in which the LytSR regulatory system responds to a collapse in ΔΨ by inducing the transcription of the lrgAB operon.