FlhE functions as a chaperone to prevent formation of periplasmic flagella in Gram-negative bacteria

The bacterial flagellum is an organelle utilized by many Gram-negative bacteria to facilitate motility. The flagellum is composed of a several {micro}m long, extracellular filament that is connected to a cytoplasmic rotor-stator complex via a periplasmic rod. Composed of [~]20 structural proteins, ranging from a few subunits to several thousand building blocks, the flagellum is a paradigm of a complex macromolecular structure that utilizes a highly regulated assembly process. This process is governed by multiple checkpoints that ensure an ordered gene expression pattern coupled to the assembly of the various flagellar building blocks in order to produce a functional flagellum. Using epifluorescence, super-resolution STED and transmission electron microscopy, we discovered that in Salmonella, the absence of one periplasmic protein, FlhE, prevents proper flagellar morphogenesis and results in the formation of periplasmic flagella. The periplasmic flagella disrupt cell wall synthesis, leading to a loss of the standard cell morphology resulting in cell lysis. We propose a model where FlhE functions as a periplasmic chaperone to control assembly of the periplasmic rod to prevent formation of periplasmic flagella. Our results highlight that bacteria evolved sophisticated regulatory mechanisms to control proper flagellar assembly and minor deviations from this highly regulated process can cause dramatic physiological consequences.