Bacterial envelope stress responses: Essential adaptors and attractive targets

Millions of deaths a year across the globe are linked to antimicrobial resistant infections. The need to develop new treatments and repurpose of existing antibiotics grows more pressing as the growing antimicrobial resistance pandemic advances. In this review article, we propose that envelope stress responses, the signaling pathways bacteria use to recognize and adapt to damage to the most vulnerable outer compartments of the microbial cell, are attractive targets. Envelope stress responses (ESRs) support colonization and infection by responding to a plethora of toxic envelope stresses encountered throughout the body; they have been co-opted into virulence networks where they work like global positioning systems to coordinate adhesion, invasion, microbial warfare, and biofilm formation. We highlight progress in the development of therapeutic strategies that target ESR signaling proteins and adaptive networks and posit that further characterization of the molecular mechanisms governing these essential niche adaptation machineries will be important for sparking new therapeutic approaches aimed at short-circuiting bacterial adaptation.