title: Investigational therapies targeting quorum-sensing for the treatment of Staphylococcus aureus infections.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories , 903 S. 4th St, 1/1110, Hamilton, MT 59840 , USA.
authors.forename: Burhan A
authors.initials: BA
authors.lastname: Khan
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Yeh
authors.forename: Gordon Y C
authors.initials: GY
authors.lastname: Cheung
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D015507:Drugs, Investigational / Q000494:pharmacology; D006801:Humans; D053038:Quorum Sensing; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents; D015507:Drugs, Investigational
keywords: Staphylococcus aureus; Staphylococcus epidermidis; quorum-sensing; quorum-sensing blockers