Investigational therapies targeting quorum-sensing for the treatment of Staphylococcus aureus infections.

INTRODUCTION: Antibiotic resistance is a serious global health concern for developed and developing nations. MRSA represents a particularly severe public health threat that is associated with high morbidity and mortality. The lack of novel antibiotics has led scientists to explore therapies targeting bacterial virulence mechanisms and virulence regulators, including those controlling cell-cell communication. AREAS COVERED: The authors discuss the role of quorum-sensing in Staphylococcus aureus infections and components of the system that are being targeted using novel investigational drugs. In particular, the authors examine the role of the accessory gene regulator (Agr) system in virulence regulation of S. aureus pathogenesis. Finally, the authors present and compare natural and synthetic compounds that have been found to interfere with Agr functionality. EXPERT OPINION: There is a great need to develop new therapeutic methods to combat S. aureus infections. These include anti-virulence therapies that target key global regulators involved with the establishment and propagation of infection. Several molecules have been found to interfere with S. aureus virulence regulation, especially those targeting the Agr quorum-sensing signaling molecule. These preliminary findings warrant further investigation and validation, with the goal of refining a compound that has broad-spectrum inhibitory effects on most S. aureus strains and Agr subtypes.