Screening of active constituents in traditional Chinese medicines as potential Salmonella Typhimurium virulence inhibitors targeting Salmonella pathogenicity island III

Abstract

Objective: To screen active constituents of traditional Chinese medicines (TCMs) as potential virulence inhibitors of Salmonella pathogenicity island III (SPI-3). Methods: The potential binding of TCM constituents to the MgtC protein of SPI-3 was clarified using molecular docking. The β-galactosidase assay was used to evaluate the effect of the TCM constituents on mgtC transcription. Finally, the effect of the drug on bacterial growth was investigated by assessing the growth curves and transcription levels of the key metabolic genes. Results: All 27 candidate TCM constituents showed that they could potentially bind to MgtC. The addition of ferulic acid, p-hydroxycinnamic acid, arctiin, and palmatine resulted in a more than 15% reduction in the transcriptional activity of mgtC. The minimum inhibitory concentrations of those four constituents on mgtC transcription were as follows: ferulic acid, 16 μM; p-hydroxycinnamic acid, 40 μM; arctiin, 80 μM; and palmatine, 160 μM. Additionally, we confirmed that none of these four constituents inhibited bacterial growth. Conclusion: In this study, we established a screening method for Salmonella virulence inhibitors based on the β-galactosidase assay, targeting SPI-3. Twenty-seven TCM constituents were screened, and four were found to have potentially potent inhibitory effects on Salmonella virulence. This provides lead compounds from herbal medicines for the development of novel antibiotics in the future. This method can also be used to screen for the virulence inhibitors of other pathogenic bacteria.

Keywords

• Salmonella Typhimurium
• Virulence inhibitor
• Salmonella pathogenicity island III
• mgtC
• Traditional Chinese medicine constituent