Elucidating the Antimicrobial Activity, Virulence, and Resistance Mechanisms of Pentabromophenol on Staphylococcus aureus

Staphylococcus aureus is a common pathogen that readily acquires antibiotic resistance and often forms biofilm, further reducing drug susceptibility. In this study, we found pentabromophenol (PBP) as an antibacterial agent with low resistance against S. aureus . PBP was identified and selected for further evaluation. Its MIC is lower than antibiotics ciprofloxacin (1 µg/mL) and tetracycline (2 µg/mL). Also, PBP dose-dependently inhibited S. aureus biofilm formation. At MIC, PBP significantly reduced bacterial growth and decreased toxin (hemolysin) production. Quantitative RT-PCR analysis revealed that PBP treatment at sub-inhibitory concentration downregulated the expression of toxin production and stress response ( hla , sigB, sarA , and psm-α ), and the two-component regulators responsible for autolysis and antibiotic resistance in S. aureus ( arlR and arlS ). PBP exposure decreased metabolic activity and increased NPN uptake, thereby decreasing cellular respiration and energy metabolism. This results in the disruption of membrane homeostasis, by proxy inhibition of the efflux system. PBP did not exhibit notable drug resistance (4-fold) for 30 passages in contrast to ciprofloxacin, with over a 1000-fold change in MIC. PBP and vancomycin combination also exhibited synergistic antimicrobial activity against S. aureus . PBP was non-toxic to HepG2 liver cells and Caenorhabditis elegans at concentrations up to 10 µg/mL (20 × MIC). These findings position PBP as a promising antimicrobial compound to combat antimicrobial resistance and biofilm-related infections owing to PBP’s high antimicrobial potency, low toxicity, and diminished propensity to develop resistance.