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.

Changes in the oligomerization potential of the division inhibitor UgtP co-ordinate Bacillus subtilis cell size with nutrient availability.

How cells co-ordinate size with growth and development is a major, unresolved question in cell biology. In previous work we identified the glucosyltransferase UgtP as a division inhibitor responsible for increasing the size of Bacillus subtilis cells under nutrient-rich conditions. In nutrient-rich medium, UgtP is distributed more or less uniformly throughout the cytoplasm and concentrated at the cell poles and/or the cytokinetic ring. Under these conditions, UgtP interacts directly with FtsZ to inhibit division and increase cell size. Conversely, under nutrient-poor conditions, UgtP is sequestered away from FtsZ in punctate foci, and division proceeds unimpeded resulting in a reduction in average cell size. Here we report that nutrient-dependent changes in UgtP's oligomerization potential serve as a molecular rheostat to precisely co-ordinate B. subtilis cell size with nutrient availability. Our data indicate UgtP interacts with itself and the essential cell division protein FtsZ in a high-affinity manner influenced in part by UDP glucose, an intracellular proxy for nutrient availability. These findings support a model in which UDP-glc-dependent changes in UgtP's oligomerization potential shift the equilibrium between UgtP•UgtP and UgtP•FtsZ, fine-tuning the amount of FtsZ available for assembly into the cytokinetic ring and with it cell size.

Cell size control in bacteria.

Like eukaryotes, bacteria must coordinate division with growth to ensure cells are the appropriate size for a given environmental condition or developmental fate. As single-celled organisms, nutrient availability is one of the strongest influences on bacterial cell size. Classic physiological experiments conducted over four decades ago first demonstrated that cell size is directly correlated with nutrient source and growth rate in the Gram-negative bacterium Salmonella typhimurium. This observation subsequently served as the basis for studies revealing a role for cell size in cell cycle progression in a closely related organism, Escherichia coli. More recently, the development of powerful genetic, molecular, and imaging tools has allowed us to identify and characterize the nutrient-dependent pathway responsible for coordinating cell division and cell size with growth rate in the Gram-positive model organism Bacillus subtilis. Here, we discuss the role of cell size in bacterial growth and development and propose a broadly applicable model for cell size control in this important and highly divergent domain of life.

A metabolic sensor governing cell size in bacteria.

Nutrient availability is one of the strongest determinants of cell size. When grown in rich media, single-celled organisms such as yeast and bacteria can be up to twice the size of their slow-growing counterparts. The ability to modulate size in a nutrient-dependent manner requires cells to: (1) detect when they have reached the appropriate mass for a given growth rate and (2) transmit this information to the division apparatus. We report the identification of a metabolic sensor that couples nutritional availability to division in Bacillus subtilis. A key component of this sensor is an effector, UgtP, which localizes to the division site in a nutrient-dependent manner and inhibits assembly of the tubulin-like cell division protein FtsZ. This sensor serves to maintain a constant ratio of FtsZ rings to cell length regardless of growth rate and ensures that cells reach the appropriate mass and complete chromosome segregation prior to cytokinesis.