Time-resolved transcriptomic analysis reveals envelope stress–mediated adaptation of Escherichia coli to the LPS transport inhibitor thanatin

We found that thanatin treatment induces a rapid activation of the Cpx envelope stress response system, followed by activation of Rcs phosphorelay and downregulation of the FlhDC regulon. Cpx regulated genes showed enrichment for pathways involved in cationic peptide resistance, stress regulation, protein folding, and peptidoglycan remodeling. Rcs upregulated genes were associated with capsule synthesis and biofilm formation.

Finally, late response to thanatin suggests the involvement of phospholipid metabolism modulation and trafficking as a strategy to restore OM asymmetry. Overall, our results delineate the adaptive mechanisms employed by bacterial cells to counteract thanatin-induced stress through an interplay of multiple regulatory pathways controlling envelope integrity, stress responses, motility and biofilm formation.