Cholesterol lipids of Borrelia burgdorferi form lipid rafts and are required for the bactericidal activity of a complement-independent antibody.
Borrelia burgdorferi, the agent of Lyme disease, is unusual as it contains free cholesterol and cholesterol glycolipids. It is also susceptible to complement-independent bactericidal antibodies, such as CB2, a monoclonal IgG1 against outer surface protein B (OspB). We find that the bactericidal action of CB2 requires the presence of cholesterol glycolipids and cholesterol. Ultrastructural, biochemical, and biophysical analysis revealed that the bacterial cholesterol glycolipids exist as lipid raft-like microdomains in the outer membrane of cultured and mouse-derived B. burgdorferi and in model membranes from B. burgdorferi lipids. The order and size of the microdomains are temperature sensitive and correlate with the bactericidal activity of CB2. This study demonstrates the existence of cholesterol-containing lipid raft-like microdomains in a prokaryote, and we suggest that the temperature dependence of B. burgdorferi lipid raft organization may have significant implications in the transmission cycle of the spirochetes which are exposed to a range of temperatures.
Department of Molecular Genetics and Microbiology, and Center for Infectious Diseases, Stony Brook University, Stony Brook, NY 11794, USA.
Timothy J
TJ
LaRocca
Jameson T
JT
Crowley
Brian J
BJ
Cusack
Priyadarshini
P
Pathak
Jordi
J
Benach
Erwin
E
London
Juan C
JC
Garcia-Monco
Jorge L
JL
Benach
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000276:immunology* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D006017:Glycolipids / Q000378:metabolism; D008193:Lyme Disease / Q000276:immunology; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D006017:Glycolipids; C077030:OspB protein, Borrelia burgdorferi; D003165:Complement System Proteins; D002784:Cholesterol