show Abstracthide AbstractMethicillin-resistant Staphylococcus aureus (MRSA) is a major threat to human health. Rather than depend on creating new antibiotics (to which bacteria will eventually become resistant), we are employing antibiotic adjuvants that potentiation existing antibiotics. Based on our previous work, loratadine, the FDA-approvide antihistamine, effectively potentiates cell-wall active antibiotics in multiple strains of MRSA. Furthermore, loratadine and oxacillin helped disrupt preformed biofilms and stop them from initially forming in vitro. A structurally related brominated carbazole, compound 8, showed similar antibiotic potentiation. To gain biological insight into these transcriptome disruptors in a more clinically relevant strain of MRSA, we used RNA-seq on treated MRSA USA100 cultures. Overall design: Differential gene expression was examined between MRSA cultures either untreated, treated with oxacillin only, treated with compound 8 or loratadine alone, or cotreated with oxacillin and loratadine or compound 8. Each of the six treatments was performed with biological triplicates.