The usnic acid derivative peziculone targets cell walls of Gram-positive bacteria revealed by high-throughput CRISPRi-seq analysis

作者：Zhang, Han; Li, Xiaojie; Liu, Xue; Ji, Xia; Ma, Xuan; Chen, Jun; Bao, Yanmin; Zhang, Yingdan; Xu, Liangxiong^*; Yang, Liang^*; Wei, Xiaoyi

来源：International Journal of Antimicrobial Agents, 2023, 62(3): 106876.

DOI：10.1016/j.ijantimicag.2023.106876

• Pezicula neosporulosa
• Usnic acid
• Peziculone
• Dibenzofuran
• Antimicrobials
• CRISPRi-seq

Usnic acid, a representative dibenzofuran metabolite, is known to have antimicrobial properties. How-ever, despite considerable interest as an antimicrobial agent, the mechanism by which usnic acid and its derivatives exert their action is not fully characterized. This article describes the synthesis of pezicu-lone, a 5:1 equilibrium mixture of two inseparable usnic acid derivatives: peziculone A and peziculone B. The antibacterial activity of peziculone against several Gram-positive bacterial pathogens was found to be significantly better compared with usnic acid. Clustered regularly interspaced short palindromic repeats interference sequencing analysis and membrane fluorescent staining were used to demonstrate that pez-iculone destabilizes the cell walls of Gram-positive bacteria. Additionally, peziculone 2.5 and 3.5 & mu;g/mL impaired cell surface appendages and biofilm formation by Staphylococcus aureus. Taken together, these data demonstrate that peziculone, a derivative compound of usnic acid, has significant antimicrobial ac-tivity against Gram-positive bacteria by targeting the cell walls; this provides a platform for development of novel antibacterial drugs. & COPY; 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy.

• 单位
  惠州学院; 中国科学院