IRON-SIRR COREGULATION OF S.EPIDERMIDIS VIRULENCE

Advanced Microbial Solutions Corporation, Milford MA

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Abstract

DESCRIPTION (provided by applicant): Iron is an important co-regulator of virulence in many bacterial species including Staphylococcus aurues and Staphylococcus epidermidis both significant human pathogens. The iron dependent transcriptional regulator DtxR [diphtheria toxin repressor] originally identified in Corynebacterium diphtheriae plays a critical role in virulence. DtxR functions as an iron sensor selectively silencing gene expression when iron is readily available. When iron levels become limiting the repressor dissociates and iron dependent genes are de-repressed. DtxR homologues can be identified in a number of gram positive pathogens including SirR in Staphylococcus epidermidis. While it is unlikely that all virulence determinants within a genera or specific species of bacteria are tied to one of these regulators it is reasonable to propose that a significant proportion rely on iron co-regulation of virulence. In Staphylococcus epidermidis both the uptake of iron from the environment and the production of bioflim appear to be at least partially regulated by the availability of iron. This proposal seeks to determine the feasibility of targeting the DtxR homologue SirR from Staphylococcus epidermidis as a potential drug target. PROPOSED COMMERCIAL APPLICATION: Direct application of existing primary to isolate iron independent SirR and test for alterations in virulence in S. epidermidis. Development of drug target to treat infections associated with medical devices. Percentage of annual $US6 billion antimicrobial drug market.