Transcriptional responses of Escherichia coli to ceragenins and antimicrobial peptides

Here we report the results of a study comparing the global transcriptional responses of Escherichia coli to two well-studied CAMPs, LL37 and colistin, and two ceragenins with related structures, CSA13 and CSA131. We found that E. coli responds similarly to both CAMPs and ceragenins by inducing a Cpx envelope stress response. However, whereas E. coli exposed to CAMPs increased expression of genes involved in colanic acid biosynthesis, bacteria exposed to ceragenins specifically modulated functions related to phosphate transport, indicating distinct mechanisms of action between these two classes of molecules. Overall, this study suggests that while some bacterial responses to ceragenins overlap with those induced by naturally-occurring CAMPs, these synthetic molecules target the bacterial envelope using a distinctive mode of action. E. coli bacteria were grown to log phase and treated with supra-MIC concentrations of antibiotics for one hour before being harvested for RNA extraction and sequencing. Data are from 3 independent experiments.