Transcriptomic Analysis of Loratadine as an Antibiotic Adjuvant Against MRSA

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved to become resistant to multiple classes of antibiotics. New antibiotics are costly to develop and deploy, and they have a limited effective lifespan. Antibiotic adjuvants are molecules that potentiate existing antibiotics through non-toxic mechanisms. We previously reported that loratadine, the active ingredient in Claritin potentiates multiple cell-wall active antibiotics in vitro and disrupts biofilm formation through a hypothesized inhibition of the master regulatory kinase Stk1. Loratadine and oxacillin combined repressed the expression of key antibiotic resistance genes in the bla and mec operons. We hypothesized that additional differentially expressed genes involved in antibiotic resistance, biofilm formation, and other cellular pathways would be modulated when looking transcriptome wide. To test this, we used RNA-seq to quantify transcript levels and found pleiotropic effects in gene expression, including genes implicated in antibiotic resistance, as well as genes critical for metabolism, transcription (RNA Polymerase subunits alpha and beta), and translation (a plethora of ribosomal protein genes and Elongation Factor Tu). Stk1 and its cognate phosphatase, stp, were also downregulated by loratadine. Together, this provides the most molecular details to date about loratadine’s function as an antibiotic adjuvant.