Design and synthesis of anti-biofilm derivatives from phospholipid amides

Bacterial biofilms serve as a natural barrier, enabling bacteria residing within them to exist and potentially amplify bacterial resistance by shielding themselves from bactericide exposure. Despite considerable efforts directed toward inhibiting bacterial growth, research has overlooked bacterial biofilms to a significant extent, leading to the frequent deficiency of traditional antimicrobials in inhibiting such biofilms. This necessitates the development of antimicrobials capable of inhibiting biofilms for effective antibacterial intervention. Herein, we have developed a new bacteriostatic agent, A₆, which has demonstrated the capability of inhibiting biofilm formation. It achieved a biofilm inhibition rate of 72.76% at a concentration of 47.94 μg/mL (2.0 EC₅₀). Mechanistic studies revealed that A₆ inhibits extracellular polymeric substances (EPS) production and bacterial motility, both critical for bacterial virulence, biofilm formation, maturation, or plant cell wall degradation. Additionally, the conductivity and protein leakage experiments demonstrated that compound A₆ significantly affected various physiological processes of Xoc. In summary, A₆ presents a promising antimicrobial solution by simultaneously inhibiting biofilms, addressing a crucial aspect of bacterial plant diseases.