| Subversion of NPC1 pathway of cholesterol transport by Anaplasma phagocytophilum. | |
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MedLine Citation:
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PMID: 22212234 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Intracellular cholesterol amounts, distribution, and traffic are tightly regulated to maintain the healthy eukaryotic cell function. However, how intracellular pathogens that require cholesterol, interact with the host cholesterol homeostasis and traffic is not well understood. Anaplasma phagocytophilum is an obligatory intracellular and cholesterol-robbing bacterium, which causes human granulocytic anaplasmosis. Here we found that a subset of cholesterol-binding membrane protein, Niemann-Pick type C1 (NPC1)-bearing vesicles devoid of lysosomal markers were upregulated in HL-60 cells infected with A. phagocytophilum, and trafficked to live bacterial inclusions. The NPC1 localization to A. phagocytophilum inclusions was abolished by low-density lipoprotein (LDL)-derived cholesterol traffic inhibitor U18666A. Studies using NPC1 siRNA and the cell line with cholesterol traffic defect demonstrated that the NPC1 function is required for bacterial cholesterol acquisition and infection. Furthermore, trans-Golgi network-specific soluble N-ethylmaleimide-sensitive factor attachment protein receptors, vesicle-associated membrane protein (VAMP4) and syntaxin 16, which are associated with NPC1 and LDL-derived cholesterol vesicular transport were recruited to A. phagocytophilum inclusions, and VAMP4 was required for bacteria infection. Taken together, A. phagocytophilum is the first example of a pathogen that subverts the NPC1 pathway of intracellular cholesterol transport and homeostasis for bacterial inclusion membrane biogenesis and cholesterol capture. |
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Authors:
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Qingming Xiong; Yasuko Rikihisa |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-29 |
Journal Detail:
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Title: Cellular microbiology Volume: - ISSN: 1462-5822 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2012-1-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100883691 Medline TA: Cell Microbiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2011 Blackwell Publishing Ltd. |
Affiliation:
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Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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