A Diguanylate Cyclase Acts as a Cell Division Inhibitor in a Two-Step Response to Reductive and Envelope Stresses

Abstract

Cell division arrest is a universal checkpoint in response to environmental assaults that generate cellular stress. In bacteria, the cyclic di-GMP (c-di-GMP) signaling network is one of several signal transduction systems that regulate key processes in response to extra-/intracellular stimuli. Here, we find that the diguanylate cyclase YfiN acts as a bifunctional protein that produces c-di-GMP in response to reductive stress and then dynamically relocates to the division site to arrest cell division in response to envelope stress in Escherichia coli. YfiN localizes to the Z ring by interacting with early division proteins and stalls cell division by preventing the initiation of septal peptidoglycan synthesis. These studies reveal a new role for a diguanylate cyclase in responding to environmental change, as well as a novel mechanism for arresting cell division.

More than Enzymes That Make or Break Cyclic Di-GMP—Local Signaling in the Interactome of GGDEF/EAL Domain Proteins of Escherichia coli

“…Instead, it relies on the increased probability of binding of c-di-GMP molecules to an effector if this c-di-GMP is produced by a local source in the immediate vicinity of the effector. Indeed, several DGCs of E. coli have been found in protein complexes with effector/target components as follows: (i) DgcM ( 13 , 14 ) and DgcE (see above) engage in a complex with PdeR and MlrA to control csgD transcription; (ii) DgcO is a member of a specific degradosome complex that also includes the c-di-GMP-controlled PNPase ( 15 , 16 ); and (iii) DgcN, when activated by transmembrane signaling, localizes to the Z-ring, where it interacts with FtsZ and ZipA to interfere with cell division ( 49 ). Identifying all c-di-GMP-binding effector/targets directly contacted by locally acting DGCs will be a challenge for future studies.…”

Signaling specificity in the c-di-GMP-dependent network regulating antibiotic synthesis in Lysobacter

“…MlrA does not bind c-di-GMP but it dissociates from the complex at high c-di-GMP concentrations, which are sensed by the ‘trigger’ PDE PdeR ( 54 , 55 ). Yet another E. coli DGC DgcN (YfiN) localizes to the cell division Z-ring, where it binds to FtsZ and ZipA proteins and inhibits cell division ( 56 ). Further, in P. aeruginosa , the DGC GcbC interact with the c-di-GMP-binding effector LapD that belongs to the class of degenerate EAL domain proteins capable of c-di-GMP binding ( 57 ).…”

Under Elevated c-di-GMP in Escherichia coli, YcgR Alters Flagellar Motor Bias and Speed Sequentially, with Additional Negative Control of the Flagellar Regulon via the Adaptor Protein RssB

“…The c-di-GMP regulators YhjH and YcgR are expressed in this bottom tier. YhjH (alternate name, PdeH [12]) is the most active PDE in E. coli and Salmonella (5,13), and YcgR is a c-di-GMP effector in both (7,14). Thus, when cells are motile, YhjH degrades c-di-GMP to keep its levels low, while YcgR arrests motor function when environmental conditions activate c-di-GMP synthesis.…”