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Abstract

Author summary The nucleotide-based second messenger c-di-GMP in bacteria controls numerous processes in response to environmental or cellular cues. Typically, these processes are related to lifestyle transitions between motile and sessile behaviors. However, c-di-GMP also regulates other processes. In Myxococcus xanthus, CdbA is a DNA-binding and nucleoid-associated protein that helps to organize the large chromosome. CdbA binds c-di-GMP and DNA in a mutually exclusive manner. While other nucleoid-associated proteins are not essential, CdbA is essential. Here, we show that the crucial function of CdbA is to maintain the level of the c-di-GMP-binding PilZ-domain protein CdbS appropriately low. The CdbS level is not only increased upon depletion of CdbA but also in response to heat stress. Under both conditions, the increased CdbS level perturbs chromosome organization and ultimately causes cell death. The CdbA/CdbS system represents a unique system that contributes to regulated cell death in M. xanthus and suggests a link between c-di-GMP signaling and regulated cell death.