Device-related infections remain a major clinical problem in patients in high-dependency units. Most of these infections are caused by coagulase-negative staphylococci, such as Staphylococcus epidermidis, which are abundant in the skin and mucous membrane microbiomes. These opportunistic pathogens owe their virulence almost entirely to their capacity to form highly antibiotic-tolerant biofilms on implanted biomaterials. Understanding biofilm production is a pre-requisite to the development of urgently needed new anti-biofilm therapeutics. Preliminary findings in the O’Gara laboratory identified an IS256 insertion mutation in an entirely novel 291bp gene, predicted to encode a hypothetical protein with significant homology to a variety of YneC/LsrG type proteins involved in the degradation of the quorum sensing homoserine lactone molecule autoinducer-2 (AI-2). The gene was designated adpS (autoinducer degrading protein of Staphylococcus). Using a clinical S. epidermidis strain CSF41498 isolated from a patient in Beaumont Hospital with a neurosurgical device-related infection, we demonstrated that overexpression of adpS on a multicopy plasmid was associated with increased biofilm formation under static and flow conditions with greater cell clustering and clumping evident. Interestingly the adpS gene does not appear to be present in the chromosomes of most S. aureus strains raising intriguing questions about its biological function. To further investigate the mechanism of AdpS-mediated biofilm regulation, this project will involve the construction and characterisation of a CSF41498 adpS mutant. In addition, the regulation of adpS will be investigated by RT-PCR. These experiments will provide new insights on biofilm-associated infections caused by these important hospital pathogens.
