Molecular mechanisms of cell–cell spread of intracellular bacterial pathogens. Issue 7 (July 2013)

• Record Type: Journal Article
• Authors: Ireton, Keith
• Is Part Of: Open biology. Volume 3:Issue 7(2013)
• Publication Date: 2013-07
• Subjects: Listeria -- Shigella -- Rickettsia -- actin-based motility -- protrusions -- cell junctions; Biology -- Periodicals; 570
• DOI: 10.1098/rsob.130079
• Languages: English
• ISSNs: 2046-2441

Abstract

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.