TY - JOUR
T1 - Selective subversion of autophagy complexes facilitates completion of the Brucella intracellular cycle
AU - Starr, Tregei
AU - Child, Robert
AU - Wehrly, Tara D.
AU - Hansen, Bryan
AU - Hwang, Seungmin
AU - López-Otin, Carlos
AU - Virgin, Herbert W.
AU - Celli, Jean
N1 - Funding Information:
We are grateful to Zijiang Zhao for his assistance in providing bone marrow from ATG5 flox/flox and ATG5 flox/flox -lyz-Cre mice, and to George Banting, Joyce Karlinsey, Tamotsu Yoshimori, Ed Miao, and Leigh Knodler for providing reagents and helpful suggestions. We thank Bob Heinzen and Leigh Knodler for critical reading of the manuscript. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, by grant U54 AI057160 to H.W.V., and by the Ministry of Science and Innovation, Spain, FP7 (Microenvimet) and the Botin Foundation to C.L.-O.
PY - 2012/1/19
Y1 - 2012/1/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84856010816&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2011.12.002
DO - 10.1016/j.chom.2011.12.002
M3 - Article
C2 - 22264511
AN - SCOPUS:84856010816
SN - 1931-3128
VL - 11
SP - 33
EP - 45
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 1
ER -