Bacteria Distinguish Between Local and Global Envelope Stress

Bacteria are small, relatively simple organisms. Their cell envelope is a multilayered structure that defines the surface of the cell, confers cell shape, and senses information about the environment. Cells also sense "stress" (e.g. mis-assembly) in the envelope - which could result from genetic, chemical, or physical perturbations - via a variety of molecular pathways. However, due to their small size, it is unknown whether bacteria can distinguish between local and global envelop stress, that is, between envelope defects at a specific location on the cell surface versus defects across the entire area of the surface. We found that a canonical envelope stress pathway (the RCS pathway) responds differently to local mechanical stress caused by growing on cell surfaces compared with global stress caused by a envelope-targeting antibiotic. By analyzing the biochemical/genetic pathway experimentally and theoretically, we discovered that the basis for the differential response was a genetic switch that elicits a discrete, additive transcriptional response in response to local and global stress as a consequence of the difference in signaling levels. This simple system illustrates a quintessentially bacterial mechanism for local, subcellular mechanosensing.