
AsianScientist (Nov. 2, 2016) – Just as a large ship is controlled by a tiny rudder, the protein MapZ can control rotational movement in bacteria. This finding, published on the cover of Science Signaling, could lead to the design of treatments that prevent the formation of biofilms.
Cyclic di-GMP (c-di-GMP) is a small molecule that controls the a wide range of bacterial behavior by binding to different protein partners. The most common protein partners are PilZ domain-containing proteins, more than 60 percent of which have only a single PilZ domain. Despite their ubiquity, the biological function and mechanism of action of many single-domain PilZ proteins remains unknown.
“We focused on the single-domain PilZ proteins because elucidating the biological function of these proteins will significantly advance our understanding of c-di-GMP signaling and close a major knowledge gap,” said corresponding author associate professor Liang Zhao-Xun from Nanyang Technological University.
While studying PilZ proteins in the opportunistic pathogen Pseudomonas aeruginosa, Liang and his team identified MapZ as a single domain PilZ protein that binds to c-di-GMP. They found that once MapZ binds to c-di-GMP, it directly interacts with CherR1, a protein that controls chemotaxis, the movement of bacteria in response to a chemical gradient.
To observe the rotation of single bacterial cells, the researchers attached the bacteria to a glass coverslip using a flagellar protein-specific antibody. They then recorded the movement of the bacteria with a video camera, producing information about the flagellar rotation speed and the frequency of switching between clockwise and counterclockwise rotations.
“The single-cell based experiments showed that the cellular abundance of MapZ controls the switching frequency of the flagellum and chemotaxis behavior. These experimental results collectively point towards an important role of MapZ in chemotaxis,” co-corresponding author assistant professor Yang Liang told Asian Scientist Magazine.
“Our study reveals a novel molecular mechanism by which c-di-GMP controls flagellar output to impact the ability of P. aeruginosa cells to attach to surfaces. Essentially, our study suggests that higher MapZ and c-di-GMP levels suppress flagellar switching and surface attachment during the early stage of biofilm formation,” he added.

In cells with low concentrations of c-di-GMP (top), CheR1 methylates the methyl-accepting chemotaxis protein (MCP) to stimulate the autokinase activity of CheA and increase the phosphorylated population of an unknown protein, X. Binding of phosphorylated X to the flagellar motor enables frequent switching between clockwise and counter clockwise rotation.
In cells with high concentrations of c-di-GMP (bottom), MapZ blocks the methylation of PctA by CheR1 to lower the autokinase activity of CheA. This decreases the population of phosphorylated X and impedes flagellar motor switching. (P, phosphoryl group; M, methyl group; SAM, S-adenosylmethionine or Ado-Met). Credit: Liang Zhao-Xun
The researchers suggest that proteins from the MapZ-associated chemotaxis pathway could be targets for biofilm inhibitors, and that engineered MapZ proteins could also potentially be used to control the movements of other types of bacteria.
“We next plan to examine how MapZ affects biofilm formation using a more biomedically relevant mouse infection model. We will also look into the potential role of MapZ in biofilm dispersal and ask the question of whether we can exploit the MapZ-associated pathway for promoting biofilm dispersal,” Yang said.
The article can be found at: Xu et al. (2016) A Cyclic di-GMP–binding Adaptor Protein Interacts with a Chemotaxis Methyltransferase to Control Flagellar Motor Switching.
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Copyright: Asian Scientist Magazine. Photo: Liang Zhao-Xun.
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