Ion Channel and Ubiquitin Differential Expression during Erythromycin-Induced Anhidrosis in Foals

SIMPLE SUMMARY: Macrolide treatment for Rhodococcus equi infections can result in severe adverse effects including hyperthermia and temporary anhidrosis. Despite these potentially lethal side effects, and a lack of understanding of the mechanisms causing them, macrolide drugs remain the recommended treatment for R. equi infections in foals. To better understand the molecular biology behind these adverse effects, we performed a differential gene expression study of skin biopsies of six healthy macrolide-treated foals experiencing anhidrosis. In total, 132 transcripts were significantly differentially expressed, and these genes belonged to functional ontologies relevant to sweat function. Genes involved in ubiquitination and ion-channel function were upregulated during the anhidrotic timepoint. These biological mechanisms play an important role in equine idiopathic anhidrosis and sweat gland function and warrant further investigation as potential targets for avoiding macrolide-induced temporary anhidrosis. ABSTRACT: Macrolide drugs are the treatment of choice for Rhodococcus equi infections, despite severe side-effects temporary anhidrosis as a. To better understand the molecular biology leading to macrolide induced anhidrosis, we performed skin biopsies and Quantitative Intradermal Terbutaline Sweat Tests (QITSTs) in six healthy pony-cross foals for three different timepoints during erythromycin administration—pre-treatment (baseline), during anhidrosis and post-recovery. RNA sequencing of biopsies followed by differential gene expression analysis compared both pre and post normal sweating timepoints to the erythromycin induced anhidrosis episode. After Bonferroni correction for multiple testing, 132 gene transcripts were significantly differentially expressed during the anhidrotic timepoint. Gene ontology analysis of the full differentially expressed gene set identified over-represented biological functions for ubiquitination and ion-channel function, both biologically relevant to sweat production. These same mechanisms were previously implicated in heritable equine idiopathic anhidrosis and sweat gland function and their involvement in macrolide-induced temporary anhidrosis warrants further investigation.