Comparison of Transcriptional Signature of Three Staphylococcal Superantigenic Toxins in Human Epidermal Melanocytes

Staphylococcus aureus, a gram‐positive bacterium, causes food poisoning and toxic shock syndrome through the production of pyrogenic toxins known as Staphylococcal enterotoxins serotypes A‐J (SEA, SEB, etc.) and toxic shock syndrome toxin‐1 (TSST‐1). A subset of these toxins have been classified as potential biothreat agents and could effectively incapacitate the soldiers on the front line. The skin model was considered appropriate for this study as the skin is the first defense barrier for the host. The purpose of this research was to identify toxin‐exclusive network‐focused trajectories sequentially perturbed across time that could potentially characterize superantigenic toxicity and early pathogenesis. Normal Human Epidermal Melanocytes were grown and treated with 25 μg/mL of one of the three toxins, SEA, SEB, and TSST‐1. Cells were collected along with viability counts after being incubated for six different time periods ranging from 0.5h to 48h. Total RNA was purified using TRIzol reagent and oligonucleotide microarrays were performed using Agilent slides containing approximately 50,000 probes. Transcriptomic expression data indicated longitudinal trajectories unique to each of the three toxins. Transcriptomic responses to both SEA and TSST‐1 treatments had similar clustering patterns where early (0.5h, 2h), middle (6h, 12h) and late (24h, 48h) time points grouped together. Interestingly, genes responding to SEB treatment followed a different clustering profile where early (0.5h, 2h) and middle (6h, 12h, 24h) time points clustered together, and the latest time point (48h) was separate. Another interesting observation is that there were no shifts in the PCA landscape between the two late time points (24h, 48h) in response to SEA and TSST‐1 treatments, but this trend was not observed for the SEB treatment, which indicated a major transcriptomic perturbation between the 24h and 48h treatments. Therefore, we concluded that at the given doses, the progression of cellular responses to SEA and TSST‐1 treatment had completed by 24h while the SEB exposure continued to affect cellular responses until 48h.We have identified distinct patterns of transcriptomic regulation for each of the SEA, SEB and TSST‐1 toxins. Many of the differentially regulated genes have important functions related to cell transformation, differentiation, apoptosis and inflammation. Work is ongoing to identify differentially regulated networks with diagnostic and therapeutic implications. Disclaimer: Research was conducted in compliance with all Federal requirements. Views expressed are those of the authors and do not constitute endorsement by the U.S. Army. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .