From Antihistamine to Anti-infective: Loratadine Inhibition of Regulatory PASTA Kinases in Staphylococci Reduces Biofilm Formation and Potentiates β-Lactam Antibiotics and Vancomycin in Resistant Strains of .

and are important human pathogens responsible for two-thirds of all postsurgical infections of indwelling medical devices. Staphylococci form robust biofilms that provide a reservoir for chronic infection, and antibiotic-resistant isolates are increasingly common in both healthcare and community settings. Novel treatments that can simultaneously inhibit biofilm formation and antibiotic-resistance pathways are urgently needed to combat the increasing rates of antibiotic-resistant infections. Herein we report that loratadine, an FDA-approved antihistamine, significantly inhibits biofilm formation in both and . Furthermore, loratadine potentiates β-lactam antibiotics in methicillin-resistant strains of and potentiates both β-lactam antibiotics and vancomycin in vancomycin-resistant strains of . Additionally, we elucidate loratadine's mechanism of action as a novel inhibitor of the regulatory PASTA kinases Stk and Stk1 in and , respectively. Finally, we describe how Stk1 inhibition affects the expression of genes involved in both biofilm formation and antibiotic resistance in and .