title: Chlamydia trachomatis utilizes the mammalian CLA1 lipid transporter to acquire host phosphatidylcholine essential for growth.
abstract: Phosphatidylcholine is a constituent of Chlamydia trachomatis membranes that must be acquired from its mammalian host to support bacterial proliferation. The CLA1 (SR-B1) receptor is a bi-directional phosphatidylcholine/cholesterol transporter that is recruited to the inclusion of Chlamydia-infected cells along with ABCA1. C. trachomatis growth was inhibited in a dose-dependent manner by BLT-1, a selective inhibitor of CLA1 function. Expression of a BLT-1-insensitive CLA1(C384S) mutant ameliorated the effect of the drug on chlamydial growth. CLA1 knockdown using shRNAs corroborated an important role for CLA1 in the growth of C. trachomatis. Trafficking of a fluorescent phosphatidylcholine analogue to Chlamydia was blocked by the inhibition of CLA1 or ABCA1 function, indicating a critical role for these transporters in phosphatidylcholine acquisition by this organism. Our analyses using a dual-labelled fluorescent phosphatidylcholine analogue and mass spectrometry showed that the phosphatidylcholine associated with isolated Chlamydia was unmodified host phosphatidylcholine. These results indicate that C. trachomatis co-opts host phospholipid transporters normally used to assemble lipoproteins to acquire host phosphatidylcholine essential for growth.
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors.forename: John V
authors.initials: JV
authors.lastname: Cox
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.|Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Yasser M
authors.initials: YM
authors.lastname: Abdelrahman
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.|Regional Biocontainment Laboratory, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Peters
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors.forename: Nirun
authors.initials: N
authors.lastname: Naher
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Belland
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002692:Chlamydia trachomatis / Q000187:drug effects / Q000254:growth & development* / Q000472:pathogenicity; D003517:Cyclopentanes / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D010713:Phosphatidylcholines / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*; D013109:Sphingomyelins / Q000378:metabolism; D013882:Thiosemicarbazones / Q000494:pharmacology
chemical_list: C526651:2-hexyl-1-cyclopentanone thiosemicarbazone; C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D003517:Cyclopentanes; D010713:Phosphatidylcholines; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D013109:Sphingomyelins; D013882:Thiosemicarbazones
keywords: ABCA1; CLA1; Chlamydia; lipid transporter; phosphatidylcholine