Staphylococcus aureus SigS induces expression of two novel short proteins that modulate its mRNA stability

Abstract

Staphylococcus aureus is an extremely successful opportunistic human pathogen, capable of causing a wide range of diseases from relatively mild skin lesions to life-threatening septicemia. This is attributed to the large arsenal of virulence factors encoded within its genome as well as the tight regulation networks that occur at multiple stages. Extracytoplasmic Function (ECF) sigma factor sigS (σs) is one of these networks that was shown to possess an important role in stress response and disease causation. Previous studies have identified and mapped transcriptional start sites for the sigS gene along with their respective promoters. However, in the literature, little to nothing is known about the genes that are governed by σs. Using RNA sequencing and Northern blot analysis, we identified two short predicted ORFs, herein as sroA and sroB, that are upregulated by SigS. We also showed that these ORFs play a role in sigS autoregulation by modulating SigS mRNA turnover. Using Bacterial Two-Hybrid Assay, we showed that SroA and SroB proteins interact with each other and SroA interacts with multiple RNA processing enzymes. Furthermore, we showed that sroA modulates the expression of multiple transcripts associated with immune evasion, antibiotic-resistant, SOS response and cell division. Collectively, our study suggests that sroA likely acts as an effector of SigS in regulating the expression of virulence factors in S. aureus.