摘要：SummaryThere are no anti-virulence and anti-biofilm treatments forStaphylococcus aureusinfection. We found that 25 μM loratadine inhibitsS. aureusbiofilm formation under static or flow-based conditions. Testing of loratadine effects on 255 clinicalS. aureusstrains 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 inS. aureuspulmonary 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 ofS. aureus. Regarding mechanism, loratadine exposure reduced RNA levels of virulence-relatedS. aureusgenes, and loratadine-induced mutations in MgrA reduced loratadine-MgrA binding. Overexpression of mutatedmgrAin wild-typeS. aureusdecreased the biofilm formation inhibition effect of loratadine.Graphical abstractDisplay OmittedHighlights•Loratadine inhibitsS. aureusbiofilm formation under static or flow conditions•Loratadine reduced mortality inS. aureuspulmonary infection model mice•Loratadine synergistically with vancomycin reduced pulmonary bacterial load•Loratadine-induced mutations in MgrA reduced loratadine-MgrA bindingDrugs; Microbiology; Microbiofilms
