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.

Messages from the first International Conference on Clinical Metagenomics (ICCMg)

“…Most of these factors have been shown to be associated with greater virulence or immune evasion in animal models of staphylococcal infections [26][27][28][29][30][31][32][33][34][35][36]. We hypothesize that lysogeny has played a significant role in increasing the ability of the ST398 clone to cause infections in humans and to become rapidly established in hospital environments.…”

Complete genome sequence analysis of the fish pathogen Flavobacterium columnare provides insights into antibiotic resistance and pathogenicity related genes

“…Fibronectin plays a major role in cell adhesion, growth, migration, and differentiation, and it is important for processes such as wound healing and embryonic development [53]. SprD (Small pathogenicity island RNA D) is a non-coding RNA expressed on pathogenicity islands in Staphylococcus aureus and significantly contribute to causing disease in an animal model [54]. Those surface structures mediating adherence and pathogen-host recognition seem to be the most important properties for the initiation of infection process in F. columnare.…”

Current knowledge on regulatory RNAs and their machineries inStaphylococcus aureus

“…Several sRNAs, named SprA-G for small pathogenicity island RNA, were identified in SaPIs. 21,31,76 The fact that the sRNAs are expressed from SaPIs, which were horizontally acquired, does not preclude that the RNA will regulate target genes located within the same locus. An example is provided by SprD, a ncRNA expressed from PIϕ.…”

“…21,29 SprD was shown to repress translation initiation of sbi mRNA encoding an immune-evasion molecule, a gene located on the core genome. 76 SprD contains four hairpin structures and the third one interacts with the ribosome binding site of the sbi mRNA to form a long duplex of 40 base pairs interrupted by bulged nucleotides. The interaction is sufficient to prevent translation initiation in vivo and has no effect on the half-life of sbi mRNA.…”