Antibacterial Activities and Action Mode of Anti-hyperlipidemic Lomitapide Against Staphylococcus aureus_1

Lomitapide has been approved by FDA for years in reducing levels of low-density lipoprotein (LDL) in cases of familial hypercholesterolemia, whereas the antibacterial effect of lomitapide remains elusive. In this study, the inhibitory activities of lomitapide against Staphylococcus aureus, including both methicillin sensitive and resistant S. aureus, were first time discovered by drug repositioning. Lomitapide has shown the inhibitory activities not only on the planktonic cell growth but also on the biofilm formation of S. aureus. Moreover, lomitapide has shown mild bactericidal effect on planktonic cells of clinical S. aureus strains as indicated in time killing assay. In order to investigate the mechanism of actions of lomitapide, quantitative proteomics analysis was then applied and suggested that the pathways involved in the cell wall biosynthesis and protein biosynthesis might participate in its action mode, whereas the clinical applications of lomitapide antibacterial activities need to be extensive investigated.