Background: The increasing threats of antibiotic resistance urge the need for developing
new approaches to combat bacterial infections including those caused by Staphylococcus
aureus (S. aureus). Unlike conventional antibiotics that aim to kill bacteria or inhibit
their growth, targeting bacterial virulence may be a promising alternative approach, which
imposes less selective pressure for antibiotic resistance in future generations.
Objective: Our goal is to provide a systematic review about developing high-throughput
screening (HTS) strategies for the identification of inhibitors targeting virulence of S. aureus.
We also describe an overview of virulence regulatory pathways for potential antivirulence
Methods: We focus on five potential targets or target families, including agr quorum sensing
system, SarA/MgrA protein family, sortase A, Clp protease and eukaryotic-like Ser/Thr
phosphatase (Stp1). For each target, we introduce its role in virulence regulation, summarize
the HTS approaches that are used to identify novel anti-virulence inhibitors, and discuss the
advantages and disadvantages of these strategies.
Conclusion: The discovery of anti-virulence inhibitors via HTS underlines the promising
potential of anti-virulence therapy for S. aureus. The development of HTS strategies can facilitate
the identification of novel anti-virulence inhibitors for combating S. aureus infection,
and may also advance our understanding on virulence regulation in S. aureus.