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Review
. 2015 Jul;17(7):951-8.
doi: 10.1111/cmi.12452. Epub 2015 May 15.

The changing nature of the Brucella-containing vacuole

Affiliations
Review

The changing nature of the Brucella-containing vacuole

Jean Celli. Cell Microbiol. 2015 Jul.

Abstract

Bacteria of the genus Brucella are intracellular vacuolar pathogens of mammals that cause the worldwide zoonosis brucellosis, and reside within phagocytes of infected hosts to promote their survival, persistence and proliferation. These traits are essential to the bacterium's ability to cause disease and have been the subject of much investigation to gain an understanding of Brucella pathogenic mechanisms. Although the endoplasmic reticulum-derived nature of the Brucella replicative niche has been long known, major strides have recently been made in deciphering the molecular mechanisms of its biogenesis, including the identification of bacterial determinants and host cellular pathways involved in this process. Here I will review and discuss the most recent advances in our knowledge of Brucella intracellular pathogenesis, with an emphasis on bacterial exploitation of the host endoplasmic reticulum-associated functions, and how autophagy-related processes contribute to the bacterium's intracellular cycle.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1. Model of Brucella intracellular trafficking in mammalian cells
Upon phagocytosis, Brucella resides within the Brucella-containing vacuole (BCV), which undergoes interactions with early endosomes (EE), late endosomes (LE) and partially fuse with lysosomes (Lys) to become the eBCV. The eBCV provides cues for induction of the VirB Type IV secretion system (T4SS), which deliver effector proteins that control eBCV interactions with ER exit sites (ERES). Activation of the UPR sensor IRE1α triggers formation of autophagic vesicles in a ATG9 and WIPI-dependent manner, that are thought to fuse with eBCV to promote rBCV biogenesis via accretion of ER-derived membranes and exclusion of endosomal membranes. The small GTPases Sar1 and Rab2 (via its interaction with the Brucella effector RicA) are required for rBCV biogenesis and subsequent bacterial replication in rBCVs. Following replication in the ER, rBCVs are converted into autophagic aBCVs via a process involving the autophagy initiation proteins Beclin1, ULK1 and ATG14L. aBCVs promote completion of the Brucella intracellular cycle by facilitating bacterial egress.

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