Caulobacter crescentus is a Gram-negative bacterium that produces two distinct progeny cells during each division cycle — a sessile stalked cell that reinitiates another round of chromosome replication, and a motile swarmer cell that cannot start DNA replication yet. Swarmer-to-stalked cell differentiation is regulated by oscillating levels of cyclic diguanylate monophosphate (c-di-GMP) and has been suggested to be linked to bacterial surface attachment. However, whether mechanical inputs can stimulate C. crescentus cell differentiation was not well understood. Two studies now provide insights into how surface contact and sensing stimulate the synthesis of c-di-GMP, which accelerates cell cycle progression and cell differentiation in C. crescentus.
In the second study Christen and colleagues investigated the molecular mechanisms connecting surface sensing to the initiation of the cell cycle in C. crescentus. They set out to identify the external signal that induces PleC and thus its downstream target PleD. They used fluorescence resonance energy transfer microscopy together with a genetically encoded c-di-GMP biosensor to monitor the levels of the second messenger in swarmer cells. Mutant cells lacking the type IV pilin PilA exhibited low c-di-GMP levels and delayed cell cycle progression compared to wild-type cells, which suggests that PilA might be an input signal for PleC. Indeed, a small N-terminal peptide sequence of PilA comprising 17 amino acids (a region the authors term cell cycle initiating pilin (CIP)) is sufficient to initiate c-di-GMP–dependent cell cycle progression. The authors showed that polymerization of PilA monomers into pilus filaments is dispensable for cell cycle initiation, which suggests that the monomeric form of PilA that is anchored in the inner membrane is the input signal. In addition, they found that the N-terminal region of PleC interacts with the CIP peptide. The authors propose a model in which surface-induced retraction of type IV pili leads to the accumulation of monomeric PilA in the inner membrane. PilA monomers subsequently interact with the transmembrane portion of the sensor kinase PleC to switch on its kinase activity, which, via a downstream c-di-GMP signalling cascade, induces chromosome replication and cell cycle progression.
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