Affiliation:
1. Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA
Abstract
Cholesterol is essential for animal cells, but most bacteria do not depend on cholesterol and instead lack cholesterol. However, the intracellular Gram-negative bacterium
Anaplasma phagocytophilum
that causes human granulocytic anaplasmosis (HGA) is unusual, as it contains significant amount of cholesterol and depends on cholesterol for survival and infection.
A. phagocytophilum
lacks genes for cholesterol biosynthesis or modification but acquire cholesterol from host cells exclusively from the LDL uptake pathway by a yet-to-be defined mechanism. Here, we uncovered a role of cholesterol-binding proteins FLOT1 and FLOT2 in LDL-derived cholesterol trafficking to
Anaplasma
inclusions and cholesterol acquisition by
Anaplasma
species. Importantly, we found that FLOTs localize to
A. phagocytophilum
-containing inclusions and the compartments containing LDL, and the acid lipase inhibitor orlistat significantly inhibits
Anaplasma
replication. Our data suggest a fundamental role of FLOTs in intracellular vesicular transport of LDL-derived free cholesterol and may provide insight regarding a new therapeutic target for HGA treatment.
Funder
HHS | NIH | National Institute of Allergy and Infectious Diseases
Publisher
American Society for Microbiology
Cited by
22 articles.
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