A deterministic, c-di-GMP-dependent program ensures the generation of phenotypically similar, symmetric daughter cells during cytokinesis

• Published in: Nature communications 2024-07, Vol.15 (1), p.6014-20, Article 6014
• Main Authors: Pérez-Burgos, María, Herfurth, Marco, Kaczmarczyk, Andreas, Harms, Andrea, Huber, Katrin, Jenal, Urs, Glatter, Timo, Søgaard-Andersen, Lotte
• Format: Article
• Language: English
• Subjects: 14/1; 14/28; 14/35; 38/35; 38/77; 631/326/1320; 631/326/41/2482; 631/326/88; 631/80/641; 82/16; 82/58; 82/80; 82/83; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Cell activation; Cell cycle; Cell Division; Cyclic GMP - analogs & derivatives; Cyclic GMP - metabolism; Cytokinesis; Cytokinesis - physiology; Daughters; Enzymes; Escherichia coli Proteins; Gene Expression Regulation, Bacterial; Heterogeneity; Humanities and Social Sciences; Motility; multidisciplinary; Myxococcus xanthus; Myxococcus xanthus - cytology; Myxococcus xanthus - genetics; Myxococcus xanthus - metabolism; Myxococcus xanthus - physiology; Phenotype; Phosphorus-Oxygen Lyases - genetics; Phosphorus-Oxygen Lyases - metabolism; Science; Science (multidisciplinary); Skewed distributions; Stochastic processes; Stochasticity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-50444-4

Phenotypic heterogeneity in bacteria can result from stochastic processes or deterministic programs. The deterministic programs often involve the versatile second messenger c-di-GMP, and give rise to daughter cells with different c-di-GMP levels by deploying c-di-GMP metabolizing enzymes asymmetrically during cell division. By contrast, less is known about how phenotypic heterogeneity is kept to a minimum. Here, we identify a deterministic c-di-GMP-dependent 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 is switched on during cytokinesis, resulting in a 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 phenotypically similar daughters with correct motility behaviours. Thus, our findings suggest a general c-di-GMP-dependent mechanism for minimizing phenotypic heterogeneity, and demonstrate that bacteria can ensure the formation of dissimilar or similar daughter cells by deploying c-di-GMP metabolizing enzymes to distinct subcellular locations. Phenotypic heterogeneity in bacteria can be generated in a programmed manner, by the asymmetrical distribution of c-di-GMP metabolizing enzymes during bacterial cell division. Here, the authors identify a c-di-GMP-dependent program with an opposite effect: the deployment and transient activation of a diguanylate cyclase at the cell division site ensures the formation of phenotypically similar daughter cells in Myxococcus xanthus .