Host cell-derived sphingolipids are required for the intracellular growth of Chlamydia trachomatis

Chlamydia trachomatis , an important cause of human disease, is an obligate intracellular bacterial pathogen that relies on the eukaryotic host cell for its replication. Recent reports have revealed that the C. trachomatis vacuole receives host-derived sphingolipids by fusing with trans -Golgi network (TGN)-derived secretory vesicles. Here, it is shown that these lipids are required for the growth of the bacteria. C. trachomatis was unable to replicate at 39°C in the Chinese hamster ovary (CHO)-derived cell line SPB-1, a cell line incapable of synthesizing sphingolipids at this temperature because of a temperature-sensitive mutation in the serine palmitoyltransferase (SPT) gene. Complementation with the wild-type SPT gene or addition of exogenous cell-permeable sphingolipid precursors to the mutant cells restored their ability to support chlamydial replication. l -cycloserine ( l -CS) and fumonisin B₁ (FB1), inhibitors of sphingolipid biosynthesis, decreased the proliferation of the bacteria in eukaryotic cells at concentrations that also decreased host cell sphingolipid synthesis. In the case of FB₁, the vacuoles appeared aberrant; the addition of sphingolipid precursors was able to reverse the altered morphology of the FB₁-treated vacuoles. Collectively, these data strongly suggest that the growth and replication of chlamydiae is dependent on synthesis of sphingolipids by the eukaryotic host cell and may contribute to this organism's obligate intracellular parasitism.