Several bacteria that replicate in the host cell’s cytosol have adopted a remarkable mechanism that depends on actin polymerization for movement. These bacteria include the human pathogens Listeria monocytogenes, Shigella flexneri, Rickettsia rickettsii (which causes Rocky Mountain spotted fever), and Burkholderia pseudomallei (which causes melioidosis, a disease characterized by severe respiratory symptoms). Baculovirus, an insect virus, also uses this mechanism for intracellular movement. All of these pathogens induce the nucleation and assembly of host-cell actin filaments at one pole of the bacterium or virus. The growing filaments generate force and push the pathogens through the cytosol at rates of up to 1 μm/sec (Figure 23–28). New filaments form at the rear of each pathogen and are left behind like a rocket trail as the microbe advances; the filaments depolymerize within a minute or so as they encounter depolymerizing factors in the cytosol. For L. monocytogenes and S. flexneri, the moving bacteria collide with the plasma membrane and move outward, inducing the formation of long, thin, host-cell protrusions with the bacteria at their tip. As shown in Figure 23–28, a neighboring cell often engulfs these projections, allowing the bacteria to enter the neighbor’s cytoplasm without exposure to the extracellular environment, thereby avoiding antibodies produced by the host’s adaptive immune system. For B. pseudomallei, movement and collision of the bacteria with the plasma membrane promotes cell–cell fusion, which serves a similar purpose of immune avoidance while allowing continued bacterial replication.
Figure 23–27 Complex strategies for viral envelope acquisition. (A) Herpesvirus nucleocapsids assemble in the nucleus and then bud through the inner nuclear membrane into the space between the inner and outer nuclear membranes, acquiring a lipid bilayer membrane coat. The virus particles then apparently lose this coat when they fuse with the endoplasmic reticulum membrane to escape into the cytosol. Subsequently, the nucleocapsids bud into the Golgi apparatus and bud out again on the other side, thereby acquiring two new membrane coats in the process. The virus then buds from the cell surface with a single membrane when its outer membrane fuses with the plasma membrane. (B) Vaccinia virus (which is closely related to the virus that causes smallpox and is used to vaccinate against smallpox) assembles in “replication factories” in the cytosol, far away from the plasma membrane. The immature virion, with one membrane, is then surrounded by two additional membranes, both acquired from the Golgi apparatus by a poorly understood wrapping mechanism, to form the intracellular enveloped virion. After fusion of the outermost membrane with the host-cell plasma membrane, the extracellular enveloped virion is released from the host cell.
Figure 23–28 The actin-based movement of bacterial pathogens within and between host cells. (A) Following invasion, bacterial pathogens such as Listeria monocytogenes, Shigella flexneri, Rickettsia rickettsii, and Burkholderia pseudomallei induce the assembly of actin-rich tails in the host-cell cytoplasm, which drives rapid bacterial movement. For most of these pathogens, the moving bacteria collide with the host-cell plasma membrane to form membrane-covered protrusions, which are engulfed by neighboring cells—spreading the infection from cell to cell. In contrast, for
B. pseudomallei, collision with the plasma membrane promotes cell–cell fusion, creating a conduit through which bacteria can invade neighboring cells (Movie 23.7).
The molecular mechanisms of pathogen-induced actin assembly differ for the different pathogens, suggesting that they evolved independently (Figure 23–29).