<i>Staphylococcus aureus</i> biofilm susceptibility to small and potent β<sup>2,2</sup>-amino acid derivatives

<div><p>Small antimicrobial β<sup>2,2</sup>-amino acid derivatives (Mw < 500 Da) are reported to display high antibacterial activity against suspended Gram-positive strains combined with low hemolytic activity. In the present study, the anti-biofilm activity of six β<sup>2,2</sup>-amino acid derivatives (<b>A1</b>–<b>A6</b>) against <i>Staphylococcus aureus</i> (ATCC 25923) was investigated. The derivatives displayed IC<sub>50</sub> values between 5.4 and 42.8 μM for inhibition of biofilm formation, and concentrations between 22.4 and 38.4 μM had substantial effects on preformed biofilms. The lead derivative <b>A2</b> showed high killing capacity (log <i>R</i>), and it caused distinct ultrastructural changes in the biofilms as shown by electron and atomic force microscopy. The anti-biofilm properties of <b>A2</b> was preserved under high salinity conditions. Extended screening showed also high activity of <b>A2</b> against <i>Escherichia coli</i> (XL1 Blue) biofilms. These advantageous features together with high activity against preformed biofilms make β<sup>2,2</sup>-amino acid derivatives a promising class of compounds for further development of anti-biofilm agents.</p></div>