From magnetosomes to vesicles: LemA proteins as drivers of bacterial membrane reorganization

The cellular machineries that remodel bacterial membranes during organelle and vesicle formation remain poorly defined. We identified MamQ as a determinant of the lipid invaginations enclosing the magnetosome. MamQ belongs to the conserved LemA protein family, whose members localize to the inner or outer membrane. Heterologous overproduction of 13 LemA proteins in Escherichia coli induced membrane restructuring and vesiculation, indicating conserved membrane-remodelling activity. In Pseudomonas aeruginosa, overproduction of the inner membrane protein LemA1 promoted cytoplasmic membrane vesicle formation, whereas the periplasmic, outer membrane-anchored LemA2 drove outer-membrane vesicle formation. Deletion of corresponding genes reduced extracellular vesicle production. Interactome analyses identified 256 partners of PaLemA1 and PaLemA2, including divisome components CpoB, FtsE, FtsI, FtsK, FtsN, FtsW, MinE, ParB, ZapG, and ZipA. Bacterial two-hybrid assays confirmed interactions between both LemA proteins and the cell division regulator CpoB, whose perturbation altered vesicle formation. Additional partners included PspA, an ESCRT-III-like protein implicated in membrane remodelling. Enriched proteins were involved in cell wall metabolism, membrane turnover, lipopolysaccharide biogenesis, protein export and maturation, energy metabolism, and stress-responsive gene regulation, suggesting that PaLemA proteins coordinate membrane-associated processes. LemA deletion mutants showed altered vesicle composition and gene expression. Furthermore, lemA2 expression was induced during stationary phase and envelope stress via the extracytoplasmic sigma factor AlgU, itself a LemA interaction partner. Our findings support the hypothesis that the LemA family acts as a hub for assembling a conserved membrane-remodelling system that, with PspA, CpoB, and divisome components, organizes membrane-localized protein complexes required for bacterial organelle biogenesis and vesicle formation.