Rickettsia parkeri invasion of diverse host cells involves an Arp2/3 complex, WAVE complex and Rho-family GTPase-dependent pathway.

Publisher: Hindawi Country of Publication: India NLM ID: 100883691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1462-5822 (Electronic) Linking ISSN: 14625814 NLM ISO Abbreviation: Cell Microbiol Subsets: MEDLINE

Publication: 2022- : Mumbai : Hindawi
Original Publication: Oxford : Wiley-Blackwell, c1999-

Actin-Related Protein 2-3 Complex/*metabolism ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/*microbiology ; Rickettsia/*pathogenicity ; Wiskott-Aldrich Syndrome Protein Family/*metabolism ; rac GTP-Binding Proteins/*metabolism; Actin Cytoskeleton/genetics ; Actin Cytoskeleton/metabolism ; Actin-Related Protein 2-3 Complex/genetics ; Animals ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; COS Cells ; Cell Line ; Chlorocebus aethiops ; Drosophila Proteins/genetics ; Drosophila melanogaster/cytology ; Drosophila melanogaster/metabolism ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Endothelial Cells/microbiology ; Fluorescent Antibody Technique ; Host-Pathogen Interactions ; Humans ; Mice ; Microbial Viability ; Plasmids/genetics ; Plasmids/metabolism ; RNA Interference ; Rickettsia/genetics ; Rickettsia/metabolism ; Rickettsia Infections/microbiology ; Signal Transduction ; Transfection ; Vero Cells ; Wiskott-Aldrich Syndrome Protein Family/genetics ; rac GTP-Binding Proteins/genetics

Rickettsiae are obligate intracellular pathogens that are transmitted to humans by arthropod vectors and cause diseases such as spotted fever and typhus. Although rickettsiae require the host cell actin cytoskeleton for invasion, the cytoskeletal proteins that mediate this process have not been completely described. To identify the host factors important during cell invasion by Rickettsia parkeri, a member of the spotted fever group (SFG), we performed an RNAi screen targeting 105 proteins in Drosophila melanogaster S2R+ cells. The screen identified 21 core proteins important for invasion, including the GTPases Rac1 and Rac2, the WAVE nucleation-promoting factor complex and the Arp2/3 complex. In mammalian cells, including endothelial cells, the natural targets of R. parkeri, the Arp2/3 complex was also crucial for invasion, while requirements for WAVE2 as well as Rho GTPases depended on the particular cell type. We propose that R. parkeri invades S2R+ arthropod cells through a primary pathway leading to actin nucleation, whereas invasion of mammalian endothelial cells occurs via redundant pathways that converge on the host Arp2/3 complex. Our results reveal a key role for the WAVE and Arp2/3 complexes, as well as a higher degree of variation than previously appreciated in actin nucleation pathways activated during Rickettsia invasion.
(© 2011 Blackwell Publishing Ltd.)

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R01 AI074760-05 United States AI NIAID NIH HHS; 5F32GM084359 United States GM NIGMS NIH HHS; R01 AI074760 United States AI NIAID NIH HHS; AI 074760 United States AI NIAID NIH HHS; F32 GM084359 United States GM NIGMS NIH HHS

0 (Actin-Related Protein 2-3 Complex)
0 (Bacterial Proteins)
0 (Drosophila Proteins)
0 (Rac1 protein, Drosophila)
0 (Wiskott-Aldrich Syndrome Protein Family)
EC 3.6.5.2 (rac GTP-Binding Proteins)

Date Created: 20111223 Date Completed: 20120628 Latest Revision: 20211021

20221213

PMC3302968

10.1111/j.1462-5822.2011.01739.x

22188208