Selective subversion of autophagy complexes facilitates completion of the Brucella intracellular cycle

Tregei Starr, Robert Child, Tara D. Wehrly, Bryan Hansen, Seungmin Hwang, Carlos López-Otin, Herbert W. Virgin, Jean Celli

Research output: Contribution to journalArticle

189 Scopus citations

Abstract

Autophagy is a cellular degradation process that can capture and eliminate intracellular microbes by delivering them to lysosomes for destruction. However, pathogens have evolved mechanisms to subvert this process. The intracellular bacterium Brucella abortus ensures its survival by forming the Brucella-containing vacuole (BCV), which traffics from the endocytic compartment to the endoplasmic reticulum (ER), where the bacterium proliferates. We show that Brucella replication in the ER is followed by BCV conversion into a compartment with autophagic features (aBCV). While Brucella trafficking to the ER was unaffected in autophagy-deficient cells, aBCV formation required the autophagy-initiation proteins ULK1, Beclin 1, and ATG14L and PI3-kinase activity. However, aBCV formation was independent of the autophagy-elongation proteins ATG5, ATG16L1, ATG4B, ATG7, and LC3B. Furthermore, aBCVs were required to complete the intracellular Brucella lifecycle and for cell-to-cell spreading, demonstrating that Brucella selectively co-opts autophagy-initiation complexes to subvert host clearance and promote infection.

Original languageEnglish
Pages (from-to)33-45
Number of pages13
JournalCell Host and Microbe
Volume11
Issue number1
DOIs
StatePublished - Jan 19 2012

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    Starr, T., Child, R., Wehrly, T. D., Hansen, B., Hwang, S., López-Otin, C., Virgin, H. W., & Celli, J. (2012). Selective subversion of autophagy complexes facilitates completion of the Brucella intracellular cycle. Cell Host and Microbe, 11(1), 33-45. https://doi.org/10.1016/j.chom.2011.12.002