Lapatinib Acts against Biofilm Formation and the Hemolytic Activity of .

Biofilm formation and hemolytic activity are closely related to the pathogenesis of infections. Herein, we show that lapatinib (12.5 μM) significantly inhibits biofilm formation and hemolytic activity of both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) isolates. Using quantitative reverse transcription PCR, we found that the RNA levels of transcriptional regulatory genes (, , , and ), biofilm-formation-related genes (, , , , and ), and virulence-related genes (, , , , , , , , , and ) of decreased after 6 h treatment with lapatinib. Wild-type isolates were continuously cultured in the presence of increasing concentrations of lapatinib for about 140 days. Subsequently, isolates with reduced susceptibility to lapatinib (the inhibitory effect of lapatinib on the biofilm formation of these isolates was significantly weakened) were selected. Mutations in the genomes of 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 .