Pyrazolone-copper complex P-FAH-Cu-phen affects transcriptome of Staphylococcus aureus

Abstract:

[Background] Staphylococcus aureus is a major bacterial pathogen causing infections in food and human body, and there is an urgent need to develop new antibacterial agents. [Objective] To study the effects of the pyrazolone-copper complex P-FAH-Cu-phen on the transcriptome and main metabolic signaling pathways of S. aureus. [Methods] The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of P-FAH-Cu-phen on S. aureus were determined by liquid dilution method. The S. aureus in the logarithmic growth phase was treated with P-FAH-Cu-phen at the final concentration of 2 μg/mL for 30 min and 2 h, respectively, and then the transcriptome was sequenced and analyzed. [Results] The MIC and MBC of P-FAH-Cu-phen on S. aureus were 2 μg/mL and 4 μg/mL, respectively. Compared with the blank control, P-FAH-Cu-phen treatment for 30 min led to 356 differentially expressed genes (DEGs), including 180 up-regulated genes and 176 down-regulated genes. P-FAH-Cu-phen treatment for 2 h resulted in 23 DEGs, including 3 up-regulated genes and 20 down-regulated genes. The DEGs were mainly enriched in membrane components, cytoplasm, plasma membrane, ATP binding, pathogenesis, metal ion binding, histidine biosynthesis process, DNA binding, hydrolytic enzyme activity, transmembrane transporter activity, nitrate assimilation, nitrate metabolism process, nitrate reductase complex, nitrate reductase activity, etc. The signaling pathways involving the DEGs mainly included two-component system, quorum sensing, nitrogen metabolism, tricarboxylic acid cycle, amino acid metabolism and so on. [Conclusion] P-FAH-Cu-phen may inhibit S. aureus by affecting plasma membrane composition, toxin production, biofilm formation, cell wall synthesis, and energy metabolism. The study provides a theoretical basis for revealing the molecular mechanism of the inhibition on S. aureus by P-FAH-Cu-phen.