Chlamydia trachomatisutilizes the mammalian CLA1 lipid transporter to acquire host phosphatidylcholine essential for growth
| Autor: | Robert J. Belland, Nirun Naher, Yasser M. AbdelRahman, Jan Peters, John V. Cox |
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| Rok vydání: | 2015 |
| Předmět: |
Thiosemicarbazones
0301 basic medicine Immunology Mutant Phospholipid Chlamydia trachomatis Cyclopentanes medicine.disease_cause Microbiology 03 medical and health sciences chemistry.chemical_compound Virology Phosphatidylcholine medicine Humans Receptor Gene knockdown biology Cell Membrane Transporter Scavenger Receptors Class B Sphingomyelins 030104 developmental biology chemistry Biochemistry ABCA1 Host-Pathogen Interactions Phosphatidylcholines biology.protein ATP Binding Cassette Transporter 1 HeLa Cells |
| Zdroj: | Cellular Microbiology. 18:305-318 |
| ISSN: | 1462-5822 1462-5814 |
| DOI: | 10.1111/cmi.12523 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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