Loratadine inhibits Staphylococcus aureus virulence and biofilm formation

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

doi:10.1016/j.isci.2022.103731

Loratadine inhibits Staphylococcus aureus virulence and biofilm formation

iScience. 2022 Jan 5;25(2):103731. doi: 10.1016/j.isci.2022.103731. eCollection 2022 Feb 18.

Authors

Jinxin Zheng¹, Yongpeng Shang¹, Yang Wu², Yuxi Zhao¹, Zhong Chen¹, Zhiwei Lin¹, Peiyu Li¹, Xiang Sun¹, Guangjian Xu¹, Zewen Wen¹, Junwen Chen¹, Yu Wang¹, Zhanwen Wang¹, Yanpeng Xiong¹, Qiwen Deng¹, Di Qu², Zhijian Yu¹

Affiliations

¹ Department of Infectious Diseases and the Key Lab of Endogenous Infection, Shenzhen Nanshan People's Hospital and The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen 518052, China.
² Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Science and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.

Abstract

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.

Keywords: Drugs; Microbiofilms; Microbiology.