title: Flipping the switch: tools for detecting small molecule inhibitors of staphylococcal virulence.
abstract: Through the expression of the accessory gene regulator quorum sensing cascade, Staphylococcus aureus is able to produce an extensive array of enzymes, hemolysins and immunomodulators essential to its ability to spread through the host tissues and cause disease. Many have argued for the discovery and development of quorum sensing inhibitors (QSIs) to augment existing antibiotics as adjuvant therapies. Here, we discuss the state-of-the-art tools that can be used to conduct screens for the identification of such QSIs. Examples include fluorescent reporters, MS-detection of autoinducing peptide production, agar plate methods for detection of hemolysins and lipase, High performance liquid chromatography-detection of hemolysins from supernatants, and cell-toxicity assays for detecting damage (or relief thereof) against human keratinocyte cells. In addition to providing a description of these various approaches, we also discuss their amenability to low-, medium-, and high-throughput screening efforts for the identification of novel QSIs.
authors.affiliation: Department of Dermatology, Emory University School of Medicine Atlanta, GA, USA ; Center for the Study of Human Health, Emory University College of Arts and Sciences Atlanta, GA, USA.
authors.forename: Cassandra L
authors.initials: CL
authors.lastname: Quave
authors.affiliation: Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Iowa City, IA, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Horswill
keywords: Staphylococcus aureus; accessory gene regulator; adjuvant therapy; auto inducing peptides; drug discovery; quorum sensing; quorum sensing inhibitor; toxins