title: Rickettsia Sca4 Reduces Vinculin-Mediated Intercellular Tension to Promote Spread.
abstract: Spotted fever group (SFG) rickettsiae are human pathogens that infect cells in the vasculature. They disseminate through host tissues by a process of cell-to-cell spread that involves protrusion formation, engulfment, and vacuolar escape. Other bacterial pathogens rely on actin-based motility to provide a physical force for spread. Here, we show that SFG species Rickettsia parkeri typically lack actin tails during spread and instead manipulate host intercellular tension and mechanotransduction to promote spread. Using transposon mutagenesis, we identified surface cell antigen 4 (Sca4) as a secreted effector of spread that specifically promotes protrusion engulfment. Sca4 interacts with the cell-adhesion protein vinculin and blocks association with vinculin's binding partner, α-catenin. Using traction and monolayer stress microscopy, we show that Sca4 reduces vinculin-dependent mechanotransduction at cell-cell junctions. Our results suggest that Sca4 relieves intercellular tension to promote protrusion engulfment, which represents a distinctive strategy for manipulating cytoskeletal force generation to enable spread.
authors: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: rlamason@berkeley.edu.
authors: Rebecca L
authors: RL
authors: Lamason
authors: Departments of Biochemistry, Microbiology, and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: Effie
authors: E
authors: Bastounis
authors: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Natasha M
authors: NM
authors: Kafai
authors: Mechanical and Aerospace Engineering Department, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Ricardo
authors: R
authors: Serrano
authors: Mechanical and Aerospace Engineering Department, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Juan C
authors: JC
authors: Del Álamo
authors: Departments of Biochemistry, Microbiology, and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: Julie A
authors: JA
authors: Theriot
authors: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: welch@berkeley.edu.
authors: Matthew D
authors: MD
authors: Welch
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D004251:DNA Transposable Elements / Q000235:genetics; D005334:Fever / Q000378:metabolism / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D040542:Mechanotransduction, Cellular; D016254:Mutagenesis, Insertional; D009154:Mutation; D012281:Rickettsia / Q000378:metabolism / Q000472:pathogenicity*; D012282:Rickettsia Infections / Q000378:metabolism* / Q000382:microbiology*; D016596:Vinculin / Q000378:metabolism*; D051178:alpha Catenin / Q000378:metabolism
chemical_list: D000199:Actins; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015820:Cadherins; D004251:DNA Transposable Elements; C488955:VCL protein, human; D051178:alpha Catenin; D016596:Vinculin
keywords: actin-based motility; cell-to-cell spread; cytoskeleton; host-pathogen interactions; intercellular tension; listeria monocytogenes; mechanotransduction; rickettsia parkeri; sca4; vinculin