Chemical and Biomolecular Insights into the <i>Staphylococcus aureus</i> Agr Quorum Sensing System: Current Progress and Ongoing Challenges

Abstract

<i>Staphylococcus aureus</i> is a ubiquitous bacterium that has become a major threat to human health due to its extensive toxin production and tremendous capacity for antibiotic resistance (e.g., MRSA "superbug" infections). Amid a worsening antibiotic resistance crisis, new strategies to combat this deadly microbe that remove the selective pressure of traditional approaches are in high demand. <i>S. aureus</i> utilizes an accessory gene regulator (<i>agr</i>) quorum sensing network to monitor its local cellular population and trigger a devastating communal attack, like an invading horde, once a threshold cell density has been reached. The role of the <i>agr</i> system in a range of disease types is still being unraveled. Herein, we discuss the present-day biochemical understanding of <i>agr</i> along with unresolved details, describe its connection to the progression of infection, and review how chemical strategies have been implemented to study and intercept this signaling pathway. This research is illuminating the potential of <i>agr</i> as an anti-virulence target in <i>S. aureus</i> and should inform the study of similar, yet less studied, <i>agr</i> systems in related bacterial pathogens.