Glyceroglycolipids are essential for Burkholderia cenocepacia intracellular survival by preventing phagolysosome acidification
Burkholderia cenocepacia is a problematic pathogen that infects people with cystic fibrosis and often causes fatal "cepacia syndrome". B. cenocepacia infection is difficult to treat due to the high intrinsic resistance of the bacterium to antimicrobials and its ability to survive in macrophages. In this study, we uncover a hitherto unknown aspect of B. cenocepacias pathogenesis related to the formation of new glyceroglycolipids, which is required for intracellular survival. Using lipidomics, we observed that B. cenocepacia can produce three glyceroglycolipid species in phosphate deplete conditions using a PlcP-mediated lipid remodelling pathway originally discovered in soil and ocean-dwelling bacteria. While lipid remodelling as an adaptation strategy for environmental microbes to cope with the scarcity of phosphorus is known, its role in intracellular bacterial survival was not investigated. Using mammalian macrophages and Galleria mellonella larvae as infection models, we showed that the mutant unable to perform membrane lipid remodelling ({Delta}plcP) could not establish infection. Unlike the wild type bacterium, the {Delta}plcP mutant did not replicate within macrophages and failed to prevent phagosome acidification. Comparative genomics analyses showed that this PlcP pathway is conserved in all pathogenic Burkholderia that infect a variety of mammalian and plant hosts. Overall, our results indicate that membrane lipid remodelling plays an essential, yet previously overlooked, role in subverting host immunity.