activities of licochalcone A against planktonic cells and biofilm of .

This study aims to evaluate the antibacterial and anti-biofilm activities of licochalcone A on and to investigate the possible target genes of licochalcone A in . This study found that licochalcone A had antibacterial activities against , with the MIC and MIC were 25 μM. Licochalcone A (at 4 × MIC) indicated a rapid bactericidal effect on planktonic cells, and killed more planktonic cells (at least 3-log cfu/ml) than vancomycin, linezolid, or ampicillin at the 2, 4, and 6 h of the time-killing test. Licochalcone A (at 10 × MIC) significantly reduced the production of persister cells (at least 2-log cfu/ml) than vancomycin, linezolid, or ampicillin at the 24, 48, 72, and 96 h of the time-killing test. Licochalcone A (at 1/4 × MIC) significantly inhibited the biofilm formation of . The RNA levels of biofilm formation-related genes, , and , markedly decreased when the isolates were treated with licochalcone A at 1/4 × MIC for 6 h. To explore the possible target genes of licochalcone A in , the licochalcone A non-sensitive clones were selected by induction of wildtype strains for about 140 days under the pressure of licochalcone A, and mutations in the possible target genes were detected by whole-genome sequencing. This study found that there were 11 nucleotide mutations leading to nonsynonymous mutations of 8 amino acids, and among these amino acid mutations, there were 3 mutations located in transcriptional regulator genes (MarR family transcriptional regulator, TetR family transcriptional regulator, and MerR family transcriptional regulator). In conclusion, this study found that licochalcone A had an antibacterial effect on , and significantly inhibited the biofilm formation of at subinhibitory concentrations.