A nutrient-dependent division antagonist is regulated post-translationally by the Clp proteases in Bacillus subtilis.

BACKGROUND: Changes in nutrient availability have dramatic and well-defined impacts on both transcription and translation in bacterial cells. At the same time, the role of post-translational control in adaptation to nutrient-poor environments is poorly understood. Previous studies demonstrate the ability of the glucosyltransferase UgtP to influence cell size in response to nutrient availability. Under nutrient-rich medium, interactions with its substrate UDP-glucose promote interactions between UgtP and the tubulin-like cell division protein FtsZ in Bacillus subtilis, inhibiting maturation of the cytokinetic ring and increasing cell size. In nutrient-poor medium, reductions in UDP-glucose availability favor UgtP oligomerization, sequestering it from FtsZ and allowing division to occur at a smaller cell mass. RESULTS: Intriguingly, in nutrient-poor conditions UgtP levels are reduced ~ 3-fold independent of UDP-glucose. B. subtilis cells cultured under different nutrient conditions indicate that UgtP accumulation is controlled through a nutrient-dependent post-translational mechanism dependent on the Clp proteases. Notably, all three B. subtilis Clp chaperones appeared able to target UgtP for degradation during growth in nutrient-poor conditions. CONCLUSIONS: Together these findings highlight conditional proteolysis as a mechanism for bacterial adaptation to a rapidly changing nutritional landscape.

An intrinsically disordered linker plays a critical role in bacterial cell division.

In bacteria, animals, fungi, and many single celled eukaryotes, division is initiated by the formation of a ring of cytoskeletal protein at the nascent division site. In bacteria, the tubulin-like GTPase FtsZ serves as the foundation for the cytokinetic ring. A conserved feature of FtsZ is an intrinsically disordered peptide known as the C-terminal linker. Chimeric experiments suggest the linker acts as a flexible boom allowing FtsZ to associate with the membrane through a conserved C-terminal domain and also modulates interactions both between FtsZ subunits and between FtsZ and modulatory proteins in the cytoplasm.

A flexible C-terminal linker is required for proper FtsZ assembly in vitro and cytokinetic ring formation in vivo.

Assembly of the cytoskeletal protein FtsZ into a ring-like structure is required for bacterial cell division. Structurally, FtsZ consists of four domains: the globular N-terminal core, a flexible linker, 8-9 conserved residues implicated in interactions with modulatory proteins, and a highly variable set of 4-10 residues at its very C terminus. Largely ignored and distinguished by lack of primary sequence conservation, the linker is presumed to be intrinsically disordered. Here we employ genetics, biochemistry and cytology to dissect the role of the linker in FtsZ function. Data from chimeric FtsZs substituting the native linker with sequences from unrelated FtsZs as well as a helical sequence from human beta-catenin indicate that while variations in the primary sequence are well tolerated, an intrinsically disordered linker is essential for Bacillus subtilis FtsZ assembly. Linker lengths ranging from 25 to 100 residues supported FtsZ assembly, but replacing the B. subtilis FtsZ linker with a 249-residue linker from Agrobacterium tumefaciens FtsZ interfered with cell division. Overall, our results support a model in which the linker acts as a flexible tether allowing FtsZ to associate with the membrane through a conserved C-terminal domain while simultaneously interacting with itself and modulatory proteins in the cytoplasm.