A Staphylococcus aureus Small RNA Is Required for Bacterial Virulence and Regulates the Expression of an Immune-Evasion Molecule

Abstract

Staphylococcus aureus, a pathogen responsible for hospital and community-acquired infections, expresses many virulence factors under the control of numerous regulatory systems. Here we show that one of the small pathogenicity island RNAs, named SprD, contributes significantly to causing disease in an animal model of infection. We have identified one of the targets of SprD and our in vivo data demonstrate that SprD negatively regulates the expression of the Sbi immune-evasion molecule, impairing both the adaptive and innate host immune responses. SprD interacts with the 5′ part of the sbi mRNA and structural mapping of SprD, its mRNA target, and the ‘SprD-mRNA’ duplex, in combination with mutational analysis, reveals the molecular details of the regulation. It demonstrates that the accessible SprD central region interacts with the sbi mRNA translational start site. We show by toeprint experiments that SprD prevents translation initiation of sbi mRNA by an antisense mechanism. SprD is a small regulatory RNA required for S. aureus pathogenicity with an identified function, although the mechanism of virulence control by the RNA is yet to be elucidated.

Author Summary

Bacteria possess numerous and diverse means of gene regulation using RNA molecules, including small RNAs (sRNAs). Here we show that one sRNA is essential for a major human bacterial pathogen, Staphylococcus aureus, to cause a disease in an animal model of infection. Our study provides evidence that this RNA regulates the expression of an immune evasion molecule secreted by the bacterium to impair the host immune responses, and we have solved the mechanism of the RNA-based regulation at molecular level. So far, the mechanism of bacterial virulence controlled by SprD is unrevealed, but that small RNA has a huge impact in the course of a bacterial infection. It implies possible new strategies in fighting against that major human and animal bacterial pathogen in preventing the expression of this regulatory RNA.