The phospholipase PlcP-mediated membrane lipid remodelling is required for the intracellular survival of Burkholderia cenocepacia.

Abstract

Burkholderia cenocepacia is a problematic pathogen that infects people with cystic fibrosis and can cause fatal "cepacia syndrome". B. cenocepacia infection is difficult to treat due to the high-level 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. cenocepacia's pathogenesis related to the formation of new glyceroglycolipids, which is involved in 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 adaptive strategy for environmental microbes to overcome phosphorus limitation is known, its role in intracellular bacterial survival has not been investigated. Using mammalian macrophages and Galleria mellonella larvae as infection models, we showed that mutants unable to perform membrane lipid remodelling (ΔplcP, Δagt) could not establish infection. Unlike the wild-type bacterium, the ΔplcP mutant did not replicate within macrophages. Comparative genomics analyses showed that this PlcP-Agt pathway is conserved in all pathogenic Burkholderia that infect mammalian and plant hosts. Overall, our results indicate that bacterial membrane lipid remodelling plays an essential role in the intracellular survival of B. cenocepacia.