Chlamydia trachomatisutilizes the mammalian CLA1 lipid transporter to acquire host phosphatidylcholine essential for growth

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Abstract

Phosphatidylcholine is a constituent ofChlamydia trachomatismembranes 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 ofChlamydia-infected cells along with ABCA1.C. trachomatisgrowth 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 ofC. trachomatis. Trafficking of a fluorescent phosphatidylcholine analogue toChlamydiawas 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 isolatedChlamydiawas unmodified host phosphatidylcholine. These results indicate thatC. trachomatisco-opts host phospholipid transporters normally used to assemble lipoproteins to acquire host phosphatidylcholine essential for growth.

The obligate intracellular pathogenChlamydia trachomatisis the leading bacterial cause of sexually transmitted infections. The growth ofChlamydiawithin infected cells is dependent upon its ability to acquire phosphatidylcholine, a major lipid in chlamydial membranes, from the host. We show thatChlamydia trachomatisco-opts the host phospholipid transporters, CLA1 and ABCA1, which are normally involved in the biogenesis of high density lipoproteins to acquire host phosphatidylcholine essential for growth. Chlamydial growth is dependent upon the lipid transport activity of CLA1. The growth ofC. trachomatis(green) within infected HeLa cells (left panel) is inhibited in cells treated with BLT-1, an inhibitor of the host CLA1 phospholipid transporter. BLT-1 exerted a similar inhibitory effect on chlamydial growth in HeLa cells transfected with a wild type CLA1-DsRed fusion (middle panel). Chlamydial growth was restored in BLT-1 treated cells that were transfected with a BLT-1 resistant mutant of CLA1, CLA1(C384S)-DsRed (right panel). Arrows point to inclusions in infected cells. Note large inclusion filled with multipleChlamydiain cell transfected with the CLA1(C384S)-DsRed mutant. Nuclei are stained with Hoechst (blue).

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