Bacteria like to move it!
January 24, 2014
IMBA Scientists reveal mechanism and dynamics of pathogen invasion of cells by 3D electron miocroscopy.
Pathogenic bacteria and viruses of several kinds, including foodborne Listeria and Shigella, have solved the problem of getting from one side of the cell to the other by hijacking the motile machinery of cells they invade to generate networks of actin filaments (comet tails) to propel themselves. While the mechanism of bacterial movement via actin fibers has been clear, details of the dynamics and the 3-D structure have been less so. In the latest issue of PLOS Biology, scientists at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences (OeAW) elucidate many of those details using the highly sophisticated technology of cryo-electron tomography and a simple but powerful model of the actin-pathogen interaction.
It has been clear for over two decades that a class of bacteria and viruses express membrane proteins that cause actin to polymerize on one side of the pathogen, forming a tail of fibers that pushes it through the cell. This mechanism is exploited by the pathogen to eject itself out of one cell into another to spread its infection.
IMBA scientists Jan Mueller and Victor Small, together with colleagues from other institutions investigated the propulsion of an insect “baculovirus” the smallest pathogen yet found to be propelled by actin. They showed that the actin filaments of the comet tail form a herringbone-like array, with filaments growing and diverging from a central core, and with the virus continually propelled forward by the growing fibers. Image analysis of electron tomograms revealed that an average of only four filaments contacted the virus at any time. Using the structural information they developed a mathematical model of propulsion from which the scientists concluded that a key stabilizing feature of the system was the pulling force exerted on the virus by a filament that is attached but not growing as fast as its neighbors. The model also showed that with too few filaments, the virus would veer rapidly and lose its course. Since larger viruses and bacteria use the same toolbox of proteins to move as baculovirus, the results described by the IMBA scientists reveal the general principles of pathogen movement through cells.
Original Publication in PloS Biology: Mueller J, Pfanzelter J, Winkler C, Narita A, Le Clainche V, et al. (2014) Electron Tomography and Simulation of Baculovirus Actin Comet Tails Support a Tethered Filament Model of Pathogen Propulsion. doi:10.1371/journal.pbio.1001765
Image: Electron tomography of baculovirus (silver cylinder in the upper right corner) reveals its propulsion mechanism through the cytoskeleton network (grey filaments) of infected cells by nucleating a fishbone-like array of branched actin filaments (colored) at the rear end.