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.
journal_name
Celljournal_title
Cellauthors
Lamason RL,Bastounis E,Kafai NM,Serrano R,Del Álamo JC,Theriot JA,Welch MDdoi
10.1016/j.cell.2016.09.023subject
Has Abstractpub_date
2016-10-20 00:00:00pages
670-683.e10issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(16)31256-9journal_volume
167pub_type
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