Genome-wide Transcription Response of Staphylococcus epidermidis to Heat Shock and Medically-Relevant Glucose Levels
Skin serves as both barrier and interface between body and environment. Skin microbes are intermediaries evolved to respond, transduce, or act in response to changing environmental or physiological conditions. Here, we quantify genome-wide changes in gene expression levels for one abundant skin commensal, Staphylococcus epidermidis, in response to an internal physiological signal, glucose levels, and an external environmental signal, temperature. We find 85 of 2354 genes change up to ~34-fold in response to medically-relevant changes in glucose concentration (0 mM to 17 mM; adj P value = 0.05). We observed carbon catabolite repression in response to a range of glucose spikes, as well as upregulation of genes involved in glucose utilization in response to persistent glucose. We observed 366 differentially expressed genes in response to a physiologically-relevant change in temperature (37°C to 45°C; adj P value = 0.05) and an S. epidermidis heat-shock response that mostly resembles the heat-shock response of related staphylococcal species. DNA motif analysis also revealed CtsR and CIRCE operator sequences arranged in tandem upstream of dnaK and groESL operons. We further identified 38 glucose-responsive genes as candidate ON or OFF genes for use in controlling synthetic genetic systems. Such systems might be used to instrument the in-situ skin microbiome or help control microbes bioengineered to serve as embedded diagnostics, monitoring, or treatment platforms. Overall design: To investigate the Staphylococcus epidermidis heat-shock response, we shifted mid-exponential phase ATCC 12228 cells from 37°C to 45°C (Sample HS). We used RNA sequencing to analyze gene expression profiles and then compared the expression profiles of heat-shocked cells to those of unstressed cells. There were three biological replicates for this experimental condition. To investigate the Staphylococcus epidermidis response to persistent glucose, we cultured ATCC 12228 cells overnight in medium supplemented with 0.2% glucose (Sample A) or 1% glucose (Sample C). There were two biological replicates for each experimental condition. We then performed gene expression profiling analysis using data from RNA-Seq. To investigate the Staphylococcus epidermidis response to medically-relevant glucose concentrations, we subjected ATCC 12228 cells to a range of 20-minute glucose spikes. Each sample (G2, G5, G10, G17, G50) represents a different glucose concentration (2 mM, 5 mM, 10 mM, 17 mM, and 50 mM respectively). G0 (0 mM) served as the control condition. There were three biological replicates for each experimental condition. We then performed gene expression profiling analysis using data from RNA-Seq. To investigate the Staphylococcus epidermidis response to a step down in glucose concentration from 10 mM to 2 mM, we subjected ATCC 12228 cells to a 10 mM glucose spike followed by a 2 mM glucose spike (sample SD). G10 (10 mM) served as the control condition. There were three biological replicates for this experimental condition. We then performed gene expression profiling analysis using data from RNA-Seq.