LAUSR

Bacterial biofilms housing dormant persister cells are innately tolerant to antibiotics and disinfectants, yet several membrane‐active agents are known to eradicate tolerant bacterial cells. NH125, a membrane‐active persister killer and starting point for development, led to the identification of two N‐arylated analogues (1 and 2) that displayed improved biofilm eradication potencies compared to the parent compound and rapid persister‐cell‐killing activities in stationary cultures of methicillin‐resistant Staphylococcus aureus (MRSA). We found 1 and 2 to be superior to other membrane‐active agents in biofilm eradication assays, with 1 demonstrating minimum biofilm eradication concentrations (MBEC) of 23.5, 11.7, and 2.35 μm against MRSA, methicillin‐resistant Staphylococcus epidermidis (MRSE), and vancomycin‐resistant Enterococcus faecium (VRE) biofilms, respectively. We tested our panel of membrane‐active agents against MRSA stationary cultures and found 1 to rapidly eradicate MRSA stationary cells by 4 log units (99.99 %) in 30 min. The potent biofilm eradication and rapid persister‐cell‐killing activities exhibited by N‐arylated NH125 analogues could have significant impact in addressing biofilm‐associated problems.