Peter Newell and a team of researchers from the Department of Microbiology and Immunology at the Dartmouth Medical School recently conducted a study uncovering the mechanism by which inorganic phosphate levels affect cell adhesion via inside-out signaling and surface protein cleavage in the cyclic dimeric GMP effector system. Their findings were published through Public Library of Science Biology.
Past studies have explored how cyclic dimeric GMP affects extracellular polymeric substance synthesis, transcription, and cell-surface protein localization in bacteria among other processes. This study investigated the response of cyclic dimeric GMP system to inorganic phosphate levels and how this affected cell adhesion.
Using a variety of procedures including biofilm, surface attachment, and activity assays, the researchers found that low inorganic phosphate levels stimulate the expression of RapA, which in turn decreases cellular cyclic dimeric GMP through its phosphodiesterase activity, causing the loss of LapA from the cell surface.
When cyclic dimeric GMP binds to LapD (an inner membrane protein), LapG (a cysteine protease) targets and cleaves amino acids at the N-terminus of LapA. As a result, LapA is released from the cell surface, breaking up bacterial biofilms, or aggregates of bacteria in which cells adhere to one another. This mechanism explains how low inorganic phosphate levels cause less cell adhesion via the cyclic dimeric GMP effector system.
Future research will continue to explore how the many proteins and other molecules of the cyclic dimeric GMP signaling pathway interact with each other.