Loratadine Interacts With MgrA and Inhibits <i>Staphylococcus aureus</i> Virulence and Biofilm Formation

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. Loratadine medical-implant coating may be an effective prophylaxis against S. aureus virulence and biofilm establishment.