Second messenger signaling in Clostridioides difficile

Small, diffusible second messenger molecules transmit information about extracellular conditions to intracellular machinery in order to influence transcription, translation, and metabolism. The enteropathogenic bacterium Clostridioides difficile coordinates its response to a dynamic and hostile environment via nucleotide second messengers. While riboswitch-mediated cyclic diguanylate regulation has been extensively characterized in C. difficile, signaling by cyclic diadenylate and by guanosine alarmones has only recently been confirmed in this organism. This review summarizes the current knowledge of how nucleotide second messenger signaling regulates physiological processes in C. difficile.