pH-dependent activation of cytokinesis modulates Escherichia coli cell size

Cell size is a complex trait, derived from both genetic and environmental factors. Environmental determinants of bacterial cell size identified to date primarily target assembly of cytosolic components of the cell division machinery. Whether certain environmental cues also impact cell size through changes in the assembly or activity of extracytoplasmic division proteins remains an open question. Here, we identify extracellular pH as a modulator of cell division and a significant determinant of cell size across evolutionarily distant bacterial species. In the Gram-negative model organism Escherichia coli, our data indicate environmental pH impacts the length at which cells divide by altering the ability of the terminal cell division protein FtsN to localize to the cytokinetic ring where it activates division. Acidic environments lead to enrichment of FtsN at the septum and activation of division at a reduced cell length. Alkaline pH inhibits FtsN localization and suppresses division activation. Altogether, our work reveals a previously unappreciated role for pH in bacterial cell size control. Author summary Bacteria are constantly under assault from endogenous and environmental stressors. To ensure viability and reproductive fitness, many bacteria alter their growth and replication in response to stressful conditions. Previous work from many groups has identified regulatory mechanisms linking cell division with nutrient availability and metabolic state. However, comparatively little is known about how the cell division machinery responds to physical and chemical cues in the environment. Here, we identify a fundamental property of the extracellular environment-environmental pH-as a significant contributor to bacterial cell size. Our genetic and cytological data indicate pH-dependent changes in E. coli cell size are in part due to differential localization of the cell division activator FtsN across pH environments. Increased abundance of FtsN at midcell in acidic environments promotes cell division at a reduced cell volume, while decreased abundance of FtsN at midcell in alkaline environments effectively delays cell division until a larger size is reached. Altogether, our work identifies pH as an environmental determinant of E. coli cell division and illuminates FtsN recruitment as a mediator of cell size.