Identification and characterization of arginine finger-like motifs, and endosome-lysosome basolateral sorting signals within the Coxiella burnetii type IV secreted effector protein CirA

Mary M Weber; Robert Faris; Erin J van Schaik; James E Samuel

doi:10.1016/j.micinf.2017.12.013

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Identification and characterization of arginine finger-like motifs, and endosome-lysosome basolateral sorting signals within the Coxiella burnetii type IV secreted effector protein CirA

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Identification and characterization of arginine finger-like motifs, and endosome-lysosome basolateral sorting signals within the Coxiella burnetii type IV secreted effector protein CirA

Mary M Weber, Robert Faris, Erin J van Schaik and James E Samuel

Microbes and infection, Vol.20(5), pp.302-307

05/2018

DOI: 10.1016/j.micinf.2017.12.013

PMCID: PMC6021133

PMID: 29331581

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Abstract

Coxiella burnetii is an obligate intracellular pathogen that replicates in an endolysosome-like compartment termed the Coxiella-containing vacuole (CCV). Formation of this unique replicative niche requires delivery of bacterial effector proteins into the host cytosol where they mediate crucial interactions with the host. We previously identified an essential Dot/Icm effector, CirA that is required for intracellular replication and CCV formation. Furthermore, CirA was shown to stimulate the GTPase activity of RhoA in vitro. In the current study, we used a bioinformatics-guided approach and identified three arginine finger-like motifs, often found in Rho GTPase-activating proteins (GAPs) and endosome-lysosome basolateral sorting signals associated with vesicle trafficking. When expressed in mammalian cells, mutation of either endosome-lysosome-basolateral sorting signals or the arginine finger-like motifs rescued stress phenotypes and decreased plasma membrane localization of ectopically expressed CirA. We further demonstrate that endosome-lysosome sorting signals are required for co-localization with Rab5 and Rab7. Collectively our data indicate that arginine finger-like motifs and endosome-lysosome-basolateral sorting signals within CirA are essential for interaction with the host cytoskeleton.

rab GTP-Binding Proteins - metabolism

Vacuoles - microbiology

Humans

Bacterial Proteins - chemistry

Bacterial Proteins - genetics

Type IV Secretion Systems - genetics

rhoA GTP-Binding Protein - metabolism

Q Fever - microbiology

Endosomes - metabolism

Coxiella burnetii - genetics

Protein Transport

Host-Pathogen Interactions

Saccharomyces cerevisiae - metabolism

Amino Acid Motifs - physiology

Coxiella burnetii - metabolism

Lysosomes - metabolism

Q Fever - metabolism

Vacuoles - metabolism

Bacterial Proteins - metabolism

Cell Membrane - metabolism

HeLa Cells

Amino Acid Motifs - genetics

Type IV Secretion Systems - metabolism

Details

Title: Subtitle: Identification and characterization of arginine finger-like motifs, and endosome-lysosome basolateral sorting signals within the Coxiella burnetii type IV secreted effector protein CirA
Creators: Mary M Weber - Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, TX, 77807, USA
Robert Faris - Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, TX, 77807, USA
Erin J van Schaik - Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, TX, 77807, USA
James E Samuel - Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College of Medicine, Bryan, TX, 77807, USA. Electronic address: jsamuel@medicine.tamhsc.edu
Resource Type: Journal article
Publication Details: Microbes and infection, Vol.20(5), pp.302-307
DOI: 10.1016/j.micinf.2017.12.013
PMID: 29331581
PMCID: PMC6021133
NLM abbreviation: Microbes Infect
ISSN: 1286-4579
eISSN: 1769-714X
Grant note: R56 AI090142 / NIAID NIH HHS R01 AI090142 / NIAID NIH HHS R21 AI088430 / NIAID NIH HHS
Language: English
Date published: 05/2018
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology
Record Identifier: 9984083885702771

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