HOST-CELL PHOSPHOLIPIDS ARE TRAFFICKED TO AND THEN MODIFIED BY CHLAMYDIA-TRACHOMATIS

There is little information on the trafficking of eukaryotic lipids fr om a host cell to either the cytoplasmic membrane of or the vacuolar m embrane surrounding intracellular pathogens. Purified Chlamydia tracho matis, an obligate intracellular bacterial parasite, contains several eukaryotic glycerophospholipids, yet attempts to demonstrate transfer of these lipids to the chlamydial cell membrane have not been successf ul. In this report, we demonstrate that eukaryotic glycerophospholipid s are trafficked from the host cell to C. trachomatis. Phospholipid tr afficking was assessed by monitoring the incorporation of radiolabelle d isoleucine, a precursor of C. trachomatis specific branched-chain fa tty acids, into host-derived glycerophospholipids and by monitoring th e transfer of host phosphatidylserine to chlamydiae and its subsequent decarboxylation to form phosphatidylethanolamine. Phospholipid traffi cking to chlamydiae was unaffected by brefeldin A, an inhibitor of Gol gi function. Furthermore, no changes in trafficking were observed when C. trachomatis was grown in a mutant cell line with a nonfunctional, nonspecific phospholipid transfer protein. Host glycerophospholipids a re modified by C. trachomatis, such that a host-synthesized straight-c hain fatty acid is replaced with a chlamydia-synthesized branched-chai n fatty acid. We also demonstrate that despite the acquisition of host -derived phospholipids, C. trachomatis is capable of de novo synthesis of phospholipids typically synthesized by prokaryotic cells. Our resu lts provide novel information on chlamydial phospholipid metabolism an d eukaryotic cell lipid trafficking, and they increase our understandi ng of the evolutionary steps leading to the establishment of an intima te metabolic association between an obligate intracellular bacterial p arasite and a eukaryotic host cell.