Lapatinib Acts against Biofilm Formation and the Hemolytic Activity of Staphylococcus aureus

[Image: see text] Biofilm formation and hemolytic activity are closely related to the pathogenesis of Staphylococcus aureus infections. Herein, we show that lapatinib (12.5 μM) significantly inhibits biofilm formation and hemolytic activity of both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates. Using quantitative reverse transcription PCR, we found that the RNA levels of transcriptional regulatory genes (RNAIII, agrA, agrC, saeR, and saeS), biofilm-formation-related genes (atl, cidA, clfA, clfB, and icaA), and virulence-related genes (cap5A, hla, hld, hlg, lukDE, lukpvl-S, staphopain B, alpha-3 PSM, beta PSM, and delta PSM) of S. aureus decreased after 6 h treatment with lapatinib. Wild-type S. aureus isolates were continuously cultured in vitro in the presence of increasing concentrations of lapatinib for about 140 days. Subsequently, S. aureus isolates with reduced susceptibility to lapatinib (the inhibitory effect of lapatinib on the biofilm formation of these S. aureus isolates was significantly weakened) were selected. Mutations in the genomes of S. aureus isolates with reduced susceptibility to lapatinib were detected by whole-genome sequencing. We identified four genes with mutations: three genes with known functions (membrane protein, pyrrolidone-carboxylate peptidase, and sensor histidine kinase LytS, respectively) and one gene with unknown function (hypothetical protein). In conclusion, this study indicates that lapatinib significantly inhibits biofilm formation and the hemolytic activity of S. aureus.