title: Molecular mechanisms of cell-cell spread of intracellular bacterial pathogens.
abstract: Several bacterial pathogens, including Listeria monocytogenes, Shigella flexneri and Rickettsia spp., have evolved mechanisms to actively spread within human tissues. Spreading is initiated by the pathogen-induced recruitment of host filamentous (F)-actin. F-actin forms a tail behind the microbe, propelling it through the cytoplasm. The motile pathogen then encounters the host plasma membrane, forming a bacterium-containing protrusion that is engulfed by an adjacent cell. Over the past two decades, much progress has been made in elucidating mechanisms of F-actin tail formation. Listeria and Shigella produce tails of branched actin filaments by subverting the host Arp2/3 complex. By contrast, Rickettsia forms tails with linear actin filaments through a bacterial mimic of eukaryotic formins. Compared with F-actin tail formation, mechanisms controlling bacterial protrusions are less well understood. However, recent findings have highlighted the importance of pathogen manipulation of host cell-cell junctions in spread. Listeria produces a soluble protein that enhances bacterial protrusions by perturbing tight junctions. Shigella protrusions are engulfed through a clathrin-mediated pathway at 'tricellular junctions'--specialized membrane regions at the intersection of three epithelial cells. This review summarizes key past findings in pathogen spread, and focuses on recent developments in actin-based motility and the formation and internalization of bacterial protrusions.
authors.affiliation: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand. keith.ireton@otago.ac.nz
authors.forename: Keith
authors.initials: K
authors.lastname: Ireton
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D005326:Fetal Proteins / Q000378:metabolism; D000080865:Formins; D054884:Host-Pathogen Interactions; D006801:Humans; D008087:Listeria / Q000502:physiology*; D008840:Microfilament Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D012281:Rickettsia / Q000502:physiology*; D012760:Shigella / Q000502:physiology*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D001426:Bacterial Proteins; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins
keywords: Listeria; Rickettsia; Shigella; actin-based motility; cell junctions; protrusions