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Abstract

Phenotypic heterogeneity in bacteria results from stochastic processes or deterministic genetic programs. These deterministic programs often incorporate the versatile second messenger c-di-GMP, and by deploying c-di-GMP metabolizing enzyme(s) asymmetrically during cell division give rise to daughter cells with different c-di-GMP levels. By contrast, less is known about how phenotypic heterogeneity is kept to a minimum. Here, we identify a deterministic c-di-GMP-dependent genetic program that is hardwired into the cell cycle of Myxococcus xanthus to minimize phenotypic heterogeneity and guarantee the formation of phenotypically similar daughter cells during division. Cells lacking the diguanylate cyclase DmxA have an aberrant motility behaviour. DmxA is recruited to the cell division site and its activity switched on during cytokinesis, resulting in a dramatic but transient increase in the c-di-GMP concentration. During cytokinesis, this c-di-GMP burst ensures the symmetric incorporation and allocation of structural motility proteins and motility regulators at the new cell poles of the two daughters, thereby generating mirror-symmetric, phenotypically similar daughters with correct motility behaviours. These findings suggest a general c-di-GMP-dependent mechanism for minimizing phenotypic heterogeneity, and demonstrate that bacteria by deploying c-di-GMP metabolizing enzymes to distinct subcellular locations ensure the formation of dissimilar or similar daughter cells.Competing Interest StatementThe authors have declared no competing interest.