The YjbH Adaptor Protein Enhances Proteolysis of the Transcriptional Regulator Spx in Staphylococcus aureus

Spx is a global regulator that is widespread among the low-GC-content Gram-positive bacteria. Spx has been extensively stud-ied in Bacillus subtilis, where it acts as an activator and a repressor of transcription in response to disulfide stress. Under non-stress conditions, Spx is rapidly degraded by the ClpXP protease. This degradation is enhanced by the YjbH adaptor protein. Upon disulfide stress, the amount of Spx rapidly increases due to a decrease in degradation. In the opportunistic pathogen Staphylococcus aureus, Spx is a global regulator influencing growth, biofilm formation, and general stress protection, and cells lacking the spx gene exhibit poor growth also under nonstress conditions. To investigate the mechanism by which the activity of Spx is regulated, we identified a homolog in S. aureus of the B. subtilis yjbH gene. The gene encodes a protein that shows ap-proximately 30 % sequence identity to YjbH of B. subtilis. Heterologous expression of S. aureus yjbH in a B. subtilis yjbHmu-tant restored Spx to wild-type levels both under nonstress conditions and under conditions of disulfide stress. From these stud-ies, we conclude that the two YjbH homologues have a conserved physiological function. Accordingly, inactivation of yjbH in S. aureus increased the level of Spx protein and transcription of the Spx-regulated gene trxB.Notably, the yjbHmutant exhibited reduced growth and increased pigmentation, and both phenotypes were reversed by complementation of the yjbH gene. All aerobic organisms encounter oxidative stress and haveevolved different ways to reduce stress-induced damage. Ox-idative stress can lead to the formation of unwanted disulfide bonds, a phenomenon known as disulfide stress (2). Spx is a tran