PLoS Pathogens · 2010 · 148 citations · 42 references
Life SciencesMicrobiologyMolecular BiologyGene ExpressionHost-pathogen InteractionsMicrobial PathogenesisBacterial PathogenesisImmune Evasion By PathogensInnate Immune ResponsePathogenicity IslandsRna-binding ProteinsVirulence Gene RegulationAntisense RnasBacterial Immune Evasion MechanismsBacterial Virulence GenesDisease VirulenceHost Defense Against Bacterial InfectionPathogenicity Island FunctionPathogenicity Island RegulationVirulence Determinants
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.
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