Host-Derived Lipids Sustain Membrane Biogenesis in an Obligate Endosymbiont

Abstract

Intracellular symbionts often undergo extreme genome reduction and lose pathways considered essential in free-living bacteria, including membrane phospholipid biosynthesis. Yet how such symbionts maintain their membranes remains poorly understood. The pea aphid Acyrthosiphon pisum harbors the obligate endosymbiont Buchnera aphidicola within specialized host cells called bacteriocytes, providing a tractable system to address this question. Here we integrated untargeted lipidomics, transcriptomics, and functional assays to investigate lipid metabolism across the symbiosis. Although Buchnera lacks nearly all canonical genes for phospholipid biosynthesis, purified Buchnera contained all major phospholipid classes detected in the host, including phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL). This repertoire differs markedly from conventional bacterial lipidomes, combining canonical bacterial phospholipids with PC, PS, and cholesterol sulfate, features more characteristic of the eukaryotic host environment. Every lipid species detected in Buchnera was also present in aphid tissues, consistent with extensive host contribution to the symbiont lipidome. Yet the Buchnera lipidome was compositionally distinct, with characteristic differences in the relative abundance of individual lipid species. Bacteriocytes were transcriptionally specialized for lipid precursor metabolism, including upregulation of phospholipid precursor synthesis and acetyl-CoA transport pathways. RNA interference targeting host lipid precursor genes reduced Buchnera abundance and disrupted symbiont morphology, linking host lipid metabolism to Buchnera maintenance. We also found that sterol availability influences Buchnera abundance. Together, these findings support a model in which host lipid metabolism sustains membrane biogenesis in a highly reduced endosymbiont and identify membrane lipids as an important dimension of metabolic integration in obligate intracellular symbioses.