Loratadine inhibits Staphylococcus aureus virulence and biofilm formation

作者：Jinxin Zheng, Yongpeng Shang, Yang Wu, Yuxi Zhao, Zhong Chen, Zhiwei Lin, Peiyu Li, Xiang Sun, Guangjian Xu, Zewen Wen, Junwen Chen, Yu Wang, Zhanwen Wang, Yanpeng Xiong, Qiwen Deng, Di Qu, Zhijian Yu · 发表于：iScience · 年份：2022 · DOI：10.1016/j.isci.2022.103731 · 被引用次数：44 · 研究领域：Antimicrobial Resistance in Staphylococcus、Bacterial biofilms and quorum sensing、Antimicrobial Peptides and Activities

There are no anti-virulence and anti-biofilm treatments for Staphylococcus aureus infection. We found that 25 μM loratadine inhibits S. aureus biofilm formation under static or flow-based conditions. Testing of loratadine effects on 255 clinical S. aureus strains with varying biofilm robustness showed inhibition of biofilm formation in medium and strong, but not weak, biofilm-producing strains. At 25 μM, loratadine reduced pigmentation and hemolysis of the bacteria without affecting growth. Loratadine (5 mg/kg) reduced mortality in S. aureus pulmonary infection model mice and acted synergistically with vancomycin to reduce pulmonary bacterial load and levels of inflammatory cytokines in bronchoalveolar lavage fluid. Loratadine analogues (side-chain carbamate moiety changed) inhibited biofilm formation, pigmentation, and hemolysis of S. aureus . Regarding mechanism, loratadine exposure reduced RNA levels of virulence-related S. aureus genes, and loratadine-induced mutations in MgrA reduced loratadine-MgrA binding. Overexpression of mutated mgrA in wild-type S. aureus decreased the biofilm formation inhibition effect of loratadine.