Summary Many studies have focused on the mechanisms underlying length and width determination in rod-shaped bacteria. Here, we focus instead on cell surface area to volume ratio (SA/V), and demonstrate that SA/V homeostasis underlies size determination. We propose a model whereby the instantaneous rates of surface and volume synthesis both scale with volume. This model predicts that these relative rates dictate SA/V and that cells approach a new steady-state SA/V exponentially, with a decay constant equal to the volume growth rate. To test this, we exposed diverse bacterial species to sublethal concentrations of a cell wall biosynthesis inhibitor and observed dose-dependent decreases in SA/V. Furthermore, this decrease was exponential and had the expected decay constant. The model also quantitatively describes SA/V alterations induced by other chemical, nutritional, and genetic perturbations. We additionally present evidence for a surface material accumulation threshold underlying division, sensitizing cell length to changes in SA/V requirements.

An immediately observable feature of bacteria is that cell size and shape are remarkably constant and characteristic for a given species in a particular condition, but vary quantitatively with physiological parameters such as growth rate, indicating both genetic and environmental regulation. However, despite decades of research, the molecular mechanisms underlying bacterial morphogenesis have remained incompletely characterized. We recently demonstrated that a wide range of bacterial species exhibit a robust surface area to volume ratio (SA/V) homeostasis. Because cell size, shape, and SA/V are mathematically interconnected, if SA/V is indeed the natural variable that cells actively monitor, this finding has critical implications for our understanding of bacterial morphogenesis, placing fundamental constraints on the sizes and shapes that cells can adopt. In this Opinion article we discuss the broad implications that this novel perspective has for the field of bacterial growth and morphogenesis.

Summary Rod-shaped bacteria typically elongate at a uniform width. To investigate the genetic and physiological determinants involved in this process, we studied a mutation in the morphogenetic protein MreB in Caulobacter crescentus that gives rise to cells with a variable-width phenotype, where cells have regions that are both thinner and wider than wild-type. During growth, individual cells develop a balance of wide and thin regions, and mutant MreB dynamically localizes to poles and thin regions. Surprisingly, the surface area to volume ratio of these irregularly-shaped cells is, on average, very similar to wild-type. We propose that, while mutant MreB localizes to thin regions and promotes rod-like growth there, wide regions develop as a compensatory mechanism, allowing cells to maintain a wild-type-like surface area to volume ratio. To support this model, we have shown that cell widening is abrogated in growth conditions that promote higher surface area to volume ratios, and we have observed individual cells with high ratios return to wild-type levels over several hours by developing wide regions, suggesting that compensation can take place at the level of individual cells.