Journal article
The Type IV Secretion System Effector Protein CirA Stimulates the GTPase Activity of RhoA and Is Required for Virulence in a Mouse Model of Coxiella burnetii Infection
Infection and immunity, Vol.84(9), pp.2524-2533
09/2016
DOI: 10.1128/IAI.01554-15
PMCID: PMC4995899
PMID: 27324482
Abstract
Coxiella burnetii, the etiological agent of Q fever in humans, is an intracellular pathogen that replicates in an acidified parasitophorous vacuole derived from host lysosomes. Generation of this replicative compartment requires effectors delivered into the host cell by the Dot/Icm type IVb secretion system. Several effectors crucial for C. burnetii intracellular replication have been identified, but the host pathways coopted by these essential effectors are poorly defined, and very little is known about how spacious vacuoles are formed and maintained. Here we demonstrate that the essential type IVb effector, CirA, stimulates GTPase activity of RhoA. Overexpression of CirA in mammalian cells results in cell rounding and stress fiber disruption, a phenotype that is rescued by overexpression of wild-type or constitutively active RhoA. Unlike other effector proteins that subvert Rho GTPases to modulate uptake, CirA is the first effector identified that is dispensable for uptake and instead recruits Rho GTPase to promote biogenesis of the bacterial vacuole. Collectively our results highlight the importance of CirA in coopting host Rho GTPases for establishment of Coxiella burnetii infection and virulence in mammalian cell culture and mouse models of infection.
Details
- Title: Subtitle
- The Type IV Secretion System Effector Protein CirA Stimulates the GTPase Activity of RhoA and Is Required for Virulence in a Mouse Model of Coxiella burnetii Infection
- Creators
- Mary M Weber - Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, Texas, USARobert Faris - Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, Texas, USAErin J van Schaik - Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, Texas, USAJuanita Thrasher McLachlan - Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, Texas, USAWilliam U Wright - Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, Texas, USAAndres Tellez - Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, Texas, USAVictor A Roman - Department of Biological Sciences, Purdue University, West Lafayette, Indiana, USAKristina Rowin - Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, Texas, USAElizabeth Di Russo Case - Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, Texas, USAZhao-Qing Luo - Department of Biological Sciences, Purdue University, West Lafayette, Indiana, USAJames E Samuel - Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, Texas, USA jsamuel@medicine.tamhsc.edu
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.84(9), pp.2524-2533
- DOI
- 10.1128/IAI.01554-15
- PMID
- 27324482
- PMCID
- PMC4995899
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Grant note
- K02 AI085403 / NIAID NIH HHS R56 AI090142 / NIAID NIH HHS R01 AI090142 / NIAID NIH HHS R21 AI088430 / NIAID NIH HHS
- Language
- English
- Date published
- 09/2016
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology
- Record Identifier
- 9984083881602771
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