Abstract
I would like to expand on one point raised by Jean Lee: how inhibiting the autoinducer of virulence, RNAIII-activating protein (RAP), can act to suppress staphylococcal infections. The expression of many virulence factors by Staphylococcus aureus is controlled by RNAIII, a regulatory RNA molecule that is encoded by the global regulatory locus agr. RNAIII can be activated by two different autoinducers: by RAP, which is agr independent[1, 2], and by an octapeptide, which is encoded by the agr locus itself[3]. Because agr is active only from the mid-exponential phase of growth, whereas RAP is continuously produced and secreted, we hypothesize that there may be a two-step rnaiii activation process (Fig. 1). During cell growth, the concentration of RAP (signal A) builds to a threshold level[1]. It then binds to its receptor, causing a cascade of events that leads to the phosphorylation of a protein called `target of RAP' (TRAP) (N. Balaban et al., unpublished). These events lead to upregulation of sarA, which then upregulates agr (Ref. [4]). Once agr is activated, agrD is expressed, and an octapeptide encoded by this gene (signal B) is produced and secreted[3]. This peptide then binds to its receptor, AgrC (Ref. [5]), resulting in its phosphorylation, in downregulation of TRAP phosphorylation (N. Balaban et al., unpublished) and in upregulation of P3 to transcribe RNAIII. RNAIII induces the genes that encode various virulence factors, leading to production of toxins. RNA-inhibiting protein (RIP) has been proposed to act as an antagonist[1], blocking RAP from binding to its receptor. Therefore, in the presence of RIP or anti-RAP antibodies, TRAP is not phosphorylated (N. Balaban et al., unpublished), the signal transduction of virulence is not activated and toxins regulated by RNAIII are not produced.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.