Anaplasma phagocytophilum Rab10-dependent parasitism of the trans-Golgi network is critical for completion of the infection cycle

Truchan, Hilary K.; VieBrock, Lauren; Cockburn, Chelsea L.; Ojogun, Nore; Griffin, Brian P.; Wijesinghe, Dayanjan S.; Chalfant, Charles E.; Carlyon, Jason A.

doi:10.1111/cmi.12500

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Anaplasma phagocytophilum Rab10-dependent parasitism of the trans-Golgi network is critical for completion of the infection cycle

2 2016
By Truchan, Hilary K. ; VieBrock, Lauren ; Cockburn, Chelsea L. ; ...
http://dx.doi.org/10.1111/cmi.12500
Source: Cell Microbiol. 18(2):260-281

[PDF-4.19 MB]

English

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Details:

Alternative Title:

Cell Microbiol
Personal Author:

Truchan, Hilary K. ; VieBrock, Lauren ; Cockburn, Chelsea L. ; Ojogun, Nore ; Griffin, Brian P. ; ... More +

Truchan, Hilary K. ; VieBrock, Lauren ; Cockburn, Chelsea L. ; Ojogun, Nore ; Griffin, Brian P. ; Wijesinghe, Dayanjan S. ; Chalfant, Charles E. ; Carlyon, Jason A. Less -
Description:

Anaplasma phagocytophilum is an emerging human pathogen and obligate intracellular bacterium. It inhabits a host cell-derived vacuole and cycles between replicative reticulate cell (RC) and infectious dense-cored (DC) morphotypes. Host-pathogen interactions that are critical for RC-to-DC conversion are undefined. We previously reported that A. phagocytophilum recruits green fluorescent protein (GFP)-tagged Rab10, a GTPase that directs exocytic traffic from the sphingolipid-rich trans-Golgi network (TGN) to its vacuole in a guanine nucleotide-independent manner. Here, we demonstrate that endogenous Rab10-positive TGN vesicles are not only routed to but also delivered into the A. phagocytophilum-occupied vacuole (ApV). Consistent with this finding, A. phagocytophilum incorporates sphingolipids while intracellular and retains them when naturally released from host cells. TGN vesicle delivery into the ApV is Rab10 dependent, up-regulates expression of the DC-specific marker, APH1235, and is critical for the production of infectious progeny. The A. phagocytophilum surface protein, uridine monophosphate kinase, was identified as a guanine nucleotide-independent, Rab10-specific ligand. These data delineate why Rab10 is important for the A. phagocytophilum infection cycle and expand the understanding of the benefits that exploiting host cell membrane traffic affords intracellular bacterial pathogens.
Subjects:

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Anaplasma Phagocytophilum Cell Line Cytoplasmic Vesicles Host-Parasite Interactions Humans Nucleoside-Phosphate Kinase Protein Binding Rab GTP-Binding Proteins Trans-Golgi Network Vacuoles
Source:

Cell Microbiol. 18(2):260-281
Pubmed ID:

26289115
Pubmed Central ID:

PMC4891814
Document Type:

Journal Article
Funding:

R01 AI072683/AI/NIAID NIH HHSUnited States/ ; R01 HL125353/HL/NHLBI NIH HHSUnited States/ ; I01 BX001792/BX/BLRD VAUnited States/ ; P30 NS047463/NS/NINDS NIH HHSUnited States/ ; R56 AI072683/AI/NIAID NIH HHSUnited States/ ; ... More +

R01 AI072683/AI/NIAID NIH HHSUnited States/ ; R01 HL125353/HL/NHLBI NIH HHSUnited States/ ; I01 BX001792/BX/BLRD VAUnited States/ ; P30 NS047463/NS/NINDS NIH HHSUnited States/ ; R56 AI072683/AI/NIAID NIH HHSUnited States/ ; P30 CA016059/CA/NCI NIH HHSUnited States/ ; R01 PH000032/PH/PHPPO CDC HHSUnited States/ ; S10 OD010641/OD/NIH HHSUnited States/ ; 5P30NS047463/NS/NINDS NIH HHSUnited States/ ; HL125353/HL/NHLBI NIH HHSUnited States/ ; UL1TR000058/TR/NCATS NIH HHSUnited States/ ; R37 AI072683/AI/NIAID NIH HHSUnited States/ ; R21 AI109068/AI/NIAID NIH HHSUnited States/ ; UL1 TR000058/TR/NCATS NIH HHSUnited States/ ; AI109068/AI/NIAID NIH HHSUnited States/ ; AI072683/AI/NIAID NIH HHSUnited States/ Less -
Volume:

18
Issue:

2
Collection(s):

CDC Public Access
Main Document Checksum:

[+]

urn:sha256:029a76b55a4b5f042e6662fe7be51efff374ccdfa658c994d0b4d331b319f4a7
Download URL:

https://stacks.cdc.gov/view/cdc/158002/cdc_158002_DS1.pdf
File Type:

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