Inhibition of Staphylococcus epidermidis Biofilm Formation by a Synthetic Breitfussin Analogue

Bacterial biofilms pose a major public health challenge by increasing the antimicrobial tolerance in pathogenic bacteria, thereby limiting the effect of medication-based treatment and promoting the development of antimicrobial resistance. Hence, there is a need to discover new molecules with the ability to prevent biofilm formation. We screened seven synthetic analogues of the breitfussin family of natural products for antimicrobial and antibiofilm activity using a broth microdilution and crystal violet method, respectively. Two compounds inhibited the growth of Gram-positive bacteria in their planktonic state at concentrations of 50 µM, of which one compound (2) demonstrated the ability to inhibit the biofilm formation of Staphylococcus epidermidis at sub-growth-inhibitory, low micromolar concentrations. Compound 2 did not inhibit biofilm growth in Staphylococcus aureus or Listeria monocytogenes, or the ability to eradicate pre-established biofilms. Initial Mode of Action (MoA) studies with compound 2 against S. epidermidis showed a modest impact on the cell surface hydrophobicity and early-stage adhesion to polystyrene. These findings highlight the breitfussin framework as a promising scaffold for the development of new antimicrobial and antibiofilm agents.