In Vitro Inhibition of Growth, Biofilm Formation, and Persisters of by Pinaverium Bromide.

Biofilm or persister cells formed by are closely related to pathogenicity. However, no antimicrobials exist to inhibit biofilm formation or persister cells induced by in clinical practice. This study found that pinaverium bromide had antibacterial activity against , with the MIC/MIC at 12.5/25 μM, respectively. Pinaverium bromide (at 4 × MIC) showed a rapid bactericidal effect on planktonic cells, and it was more effective (at least 1-log cfu/mL) than linezolid, vancomycin, and ampicillin at 4 h of the time-killing test. Pinaverium bromide (at 10 × MIC) significantly inhibited the formation of persister cells (at least 3-log cfu/mL) than linezolid, vancomycin, and ampicillin at 24, 48, 72, 96, and 120 h of the time-killing test. Biofilm formation and adherent cells of isolates were significantly inhibited by pinaverium bromide (at 1/2 or 1/4 × MICs). The fluorescence intensity of the membrane polarity of increased with the treatment of pinaverium bromide (≥1 × MIC), and the MICs of pinaverium bromide increased by 4 times with the addition of cell membrane phospholipids, phosphatidyl glycerol and cardiolipin. The cell viabilities of human hepatocellular carcinoma cells HepG2 and Huh7, mouse monocyte-macrophage cells J774, and human hepatic stellate cells LX-2 were slightly inhibited by pinaverium bromide (<50 μM). There were 54 different abundance proteins detected in the pinaverium bromide-treated isolate by proteomics analysis, of which 33 proteins increased, whereas 21 proteins decreased. The abundance of superoxide dismutase sodM and ica locus proteins icaA and icaB decreased. While the abundance of global transcriptional regulator spxA and Gamma-hemolysin component B increased. In conclusion, pinaverium bromide had an antibacterial effect on and significantly inhibited the formation of biofilm and persister cells of .