A Farnesylated Coxiella Burnetii Effector Forms a Multimeric Complex at the Mitochondrial Outer Membrane During Infection

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2017 Mar 1

PMID 28242621

Citations 13

Authors

Laura F Fielden

Jennifer H Moffatt

Yilin Kang

Michael J Baker

Chen Ai Khoo

Craig R Roy

Diana Stojanovski

Hayley J Newton

Affiliations

Soon will be listed here.

Abstract

, the causative agent of Q fever, establishes a unique lysosome-derived intracellular niche termed the -containing vacuole (CCV). The Dot/Icm-type IVB secretion system is essential for the biogenesis of the CCV and the intracellular replication of Effector proteins, translocated into the host cell through this apparatus, act to modulate host trafficking and signaling processes to facilitate CCV development. Here we investigated the role of CBU0077, a conserved effector that had previously been observed to localize to lysosomal membranes. CBU0077 was dispensable for the intracellular replication of in HeLa and THP-1 cells and did not appear to participate in CCV biogenesis. Intriguingly, native and epitope-tagged CBU0077 produced by displayed specific punctate localization at host cell mitochondria. As such, we designated CBU0077 MceA (itochondrial ffector protein ). Analysis of ectopically expressed MceA truncations revealed that the capacity to traffic to mitochondria is encoded within the first 84 amino acids of this protein. MceA is farnesylated by the host cell; however, this does not impact mitochondrial localization. Examination of mitochondria isolated from infected cells revealed that MceA is specifically integrated into the mitochondrial outer membrane and forms a complex of approximately 120 kDa. Engineering to express either MceA tagged with 3×FLAG or MceA tagged with 2×hemagglutinin allowed us to perform immunoprecipitation experiments that showed that MceA forms a homo-oligomeric species at the mitochondrial outer membrane during infection. This research reveals that mitochondria are a bona fide target of effectors and MceA is a complex-forming effector at the mitochondrial outer membrane during infection.

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