M. Campbell, Chih-Yun Cho, A. Ho
Jul 11, 2020
Citations
0
Influential Citations
10
Citations
Quality indicators
Journal
International journal of antimicrobial agents
Abstract
The adverse health effects of Staphylococcus aureus biofilm infections coupled with an increased global prevalence of antibiotic resistance highlight the need for novel anti-pathogenic, anti-biofilm compounds. We recently determined that ethyl-4-ethoxybenzoic acid (EEB) had anti-pathogenic, anti-biofilm activity. Based on this finding, we carried out a structure-activity analysis to identify more effective compounds. Microtiter crystal violet assays followed by plate counts, were conducted to measure the dose-dependent anti-biofilm and antimicrobial activities of 13 phenolic compounds related to EEB. By displaying these characteristics on a two-component plot, we identified 4-ethoxybenzoic acid (4EB) and methyl gallate as two anti-pathogenic, anti-biofilm compounds of interest. To characterize their mechanisms of activity we examined their effects on cell hydrophobicity, hemolysis, membrane integrity, extracellular polymeric substance (EPS) production and vancomycin sensitivity. Both 4EB and methyl gallate inhibited up to 87 percent biofilm formation with minimal impact on the viability of stationary phase cells or bacterial growth. Combination treatments of 4-ethoxybenxoic acid and vancomycin decreased the viability of biofilm dwelling cells up to 85 percent when compared to vancomycin alone indicating a synergistic effect. Methyl gallate did not potentiate vancomycin. 4EB decreased the percentage of hydrophobic cells in culture from 78 to 49 percent indicating that 4EB may prevent biofilm formation by altering cell membrane hydrophobicity. Our findings suggest that 4EB has potential as an anti-pathogenic, anti-biofilm agent for the prevention of S. aureus biofilms or as a treatment for established biofilms when combined with antibiotics.