Lannoy Adélie, Ronneau Alexi, Fernández-García Miguel, Dieu Marc, Renard Patricia, García Fernández Antonia, Condez-Alvarez Raquel, De Bolle Xavier
URBM and Department of Biology, Namur Research Institute for Life Sciences (NARILIS), Namur, Belgium.
Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660, Boadilla del Monte, Spain.
EMBO J. 2025 Aug 13. doi: 10.1038/s44318-025-00511-3.
The cell envelope of gram-negative bacteria is composed of an inner and an outer membrane. In Escherichia coli, several pathways mediate phospholipid transport between the two membranes, including the Mla (i.e., maintenance of lipid asymmetry) and Pqi (i.e., paraquat inducible) systems. Here, we identify and characterise in the intracellular pathogen Brucella abortus a complex named Mpc, which exhibits homology to both Mla and Pqi components. Mpc is required for bacterial growth under envelope stress conditions, and for survival within macrophages during the early stages of infection. Analyses of protein-protein interactions and structural predictions suggest that the Mpc complex bridges the two membranes of the bacterial cell envelope. Absence of this system results in altered lipid composition of the outer membrane vesicles, indicating that Mpc plays a role in lipid transport between the membranes. Our sequence comparisons reveal that Mpc is conserved across numerous species of Hyphomicrobiales. The discovery of this novel lipid-trafficking system expands our understanding of the diversity and evolution of lipid-transport mechanisms in diderm bacteria.
革兰氏阴性菌的细胞包膜由内膜和外膜组成。在大肠杆菌中,有几种途径介导两膜之间的磷脂转运,包括Mla(即维持脂质不对称性)和Pqi(即百草枯诱导)系统。在此,我们在细胞内病原体布鲁氏菌中鉴定并表征了一个名为Mpc的复合体,它与Mla和Pqi组分均具有同源性。Mpc是细菌在包膜应激条件下生长以及在感染早期阶段于巨噬细胞内存活所必需的。蛋白质-蛋白质相互作用分析和结构预测表明,Mpc复合体连接细菌细胞包膜的两膜。该系统缺失会导致外膜囊泡的脂质组成改变,表明Mpc在膜间脂质转运中发挥作用。我们的序列比较显示,Mpc在许多丝状杆菌目物种中保守。这一新的脂质转运系统的发现扩展了我们对双膜细菌脂质转运机制的多样性和进化的理解。