The Gram-negative bacterial cell envelope is a complex structure and its homeostasis is essential for bacterial survival. Envelope stress responses (ESRs) are signal transduction pathways that monitor the fidelity of envelope assembly during normal growth and also detect and repair envelope damage caused by external assaults, including immune factors, protein toxins, and antibiotics. In this review, we focus on three best-studied ESRs and discuss the mechanisms by which ESRs detect various perturbations of envelope assembly and integrity and regulate envelope remodeling to promote bacterial survival. We will highlight the complex relationship of ESRs with envelope biogenesis pathways and discuss some of the challenges in this field on the road to mapping the global regulatory network of envelope homeostasis.
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