Li Li, Xu Zuxian, Cao Ruipin, Li Jiaxin, Wu Chang-Jer, Wang Yinglu, Zhu Hu
Fujian-Taiwan Science and Technology Cooperation Base of Biomedical Materials and Tissue Engineering, Engineering Research Center of Industrial Biocatalysis, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fujian Provincial Key Laboratory of Polymer Materials, College of Chemistry and Materials Science, Fujian Normal University, Fuzhou 350007, China.
Department of Food Science, National Taiwan Ocean University, Keelung 20224, Taiwan.
iScience. 2023 Jun 7;26(7):107048. doi: 10.1016/j.isci.2023.107048. eCollection 2023 Jul 21.
We investigated the influence of hydroxyl groups on the anti-quorum-sensing (anti-QS) and anti-biofilm activity of structurally similar cyclic dipeptides, namely cyclo(-Pro--Tyr), cyclo(-Hyp--Tyr), and cyclo(-Pro--Phe), against PAO1. Cyclo(-Pro--Phe), lacking hydroxyl groups, displayed higher virulence factor inhibition and cytotoxicity, but showed less inhibitory ability in biofilm formation. Cyclo(-Pro--Tyr) and cyclo(-Hyp--Tyr) suppressed genes in both the and systems, whereas cyclo(-Pro--Phe) mainly downregulated I and R expression. These cyclic dipeptides interacted with the QS-related protein LasR, with similar binding efficiency to the autoinducer 3OC12-HSL, except for cyclo(-Pro--Phe) which had lower affinity. In addition, the introduction of hydroxyl groups significantly improved the self-assembly ability of these peptides. Both cyclo(-Pro--Tyr) and cyclo(-Hyp--Tyr) formed assembly particles at the highest tested concentration. The findings revealed the structure-function relationship of this kind of cyclic dipeptides and provided basis for our follow-up research in the design and modification of anti-QS compounds.
我们研究了羟基对结构相似的环二肽（即环（-脯氨酸-酪氨酸）、环（-羟脯氨酸-酪氨酸）和环（-脯氨酸-苯丙氨酸））针对铜绿假单胞菌PAO1的群体感应抑制（抗QS）和抗生物膜活性的影响。缺乏羟基的环（-脯氨酸-苯丙氨酸）表现出更高的毒力因子抑制作用和细胞毒性，但在生物膜形成方面的抑制能力较弱。环（-脯氨酸-酪氨酸）和环（-羟脯氨酸-酪氨酸）抑制了两个系统中的基因，而环（-脯氨酸-苯丙氨酸）主要下调I和R的表达。这些环二肽与群体感应相关蛋白LasR相互作用，除了亲和力较低的环（-脯氨酸-苯丙氨酸）外，它们与自诱导物3OC12-HSL的结合效率相似。此外，羟基的引入显著提高了这些肽的自组装能力。环（-脯氨酸-酪氨酸）和环（-羟脯氨酸-酪氨酸）在最高测试浓度下均形成了组装颗粒。这些发现揭示了这类环二肽的结构-功能关系，并为我们后续抗QS化合物的设计和修饰研究提供了依据。
