Inhibition of Rho Activity Increases Expression of SaeRS-Dependent Virulence Factor Genes in Staphylococcus aureus, Showing a Link between Transcription Termination, Antibiotic Action, and Virulence

Abstract

The major human pathogen Staphylococcus aureus is a widespread commensal bacterium but also the most common cause of nosocomial infections. It adapts to the different host niches through a complex gene regulatory network. We show here that the Rho transcription termination factor, which represses pervasive antisense transcription in various bacteria, including S. aureus, plays a role in controlling SaeRS-dependent virulence gene expression. A Rho-deficient strain produces larger amounts of secreted virulence factors in vitro and shows increased virulence in mice. We also show that treatment of S. aureus with the antibiotic bicyclomycin, which inhibits Rho activity and is effective against Gram-negative bacteria, induces the same changes in the proteome as observed in the Rho-deficient strain. Our results reveal for the first time a link between transcription termination and virulence regulation in S. aureus, which implies a novel mechanism by which an antibiotic can modulate the expression of virulence factors.

Metabolic Cross-talk Between Human Bronchial Epithelial Cells and Internalized Staphylococcus aureus as a Driver for Infection*

“…All samples were resuspended in a buffer consisting of 2% acetonitrile and 0.1% acetic acid in MS-grade water. Indexed Retention Time The S. aureus ion library used in this study was generated previously (32). Briefly, the data sets used for the construction of this library comprise samples of the cytosolic and exoproteomes of S. aureus HG001 and the isogenic Δrho mutant ST1258.…”

A Truncated Galectin-3 Isolated from Skin Mucus of Atlantic Salmon Salmo salar Binds to and Modulates the Proteome of the Gram-Negative Bacteria Moritella viscosa

“…Transcription termination factor Rho is as the name says involved in termination of transcription, it is targeted by the antibiotics bicyclomycin. Interestingly, knock down of Rho has been linked to increased Staphylococcus aureus virulence [37], indicating that bacteria under less favrable conditions increase their virulence after Rho silicing.…”

Interaction of Staphylococcus aureus and Host Cells upon Infection of Bronchial Epithelium during Different Stages of Regeneration

“…Proteins were identified and quantified using Spectronaut V11.0.18108.11.30271 software (Biognosys AG) against MS databases generated from data-dependent acquisition (DDA) measurements of either S. aureus ( 31 ) or epithelial cells 27 under different culture conditions. The bacterial ion library was constructed on the basis of the fasta file from AureoWiki 54 with 2.852 S. aureus protein entries, from which the final target–decoy version was generated by adding all reverse entries to a total of 5.944 entries.…”

“…The annotation of identified proteins was based on the Uniprot database. For S. aureus , the annotation was complemented with the AureoWiki database 54 and the regulons as described by Nagel et al 31 The latter was used as a database to draw Voronoi tree maps using the Paver 2.1 software (DECODON GmbH, Greifswald, Germany).…”