Antibacterial and Antibiofilm Activities of Sertindole and Its Antibacterial Mechanism against Staphylococcus aureus

[Image: see text] As methicillin-resistant Staphylococcus aureus has become the most prevalent antibiotic-resistant pathogen in many countries, there is an urgent demand to develop novel antibacterial agents. The purpose of this study is to investigate sertindole’s antibacterial and antibiofilm properties, as well as its antibacterial mechanism against S. aureus. The MIC(50) and MIC(90) values for sertindole against S. aureus were both determined to be 50 μM, and sertindole significantly reduced S. aureus growth at a subinhibitory concentration of 1/2× MIC. Sertindole also showed remarkable potency in inhibiting the development of biofilms. Additionally, proteomic analysis revealed that sertindole could dramatically decrease the biosynthesis of amino acids and trigger the cell wall stress response and oxidative stress response. A series of tests, including membrane permeability assays, quantitative real-time reverse transcription-PCR, and electron microscope observations, revealed that sertindole disrupts cell integrity. The two-component system VraS/VraR knockout S. epidermis strain also showed enhanced sensitivity to sertindole. Overall, our data suggested that sertindole exhibited antibacterial and biofilm-inhibiting activities against S. aureus and that its antibacterial actions may involve the destruction of cell integrity.