Work

Salmonella encodes murein lipoproteins differing in the anchoring to peptidoglycan and intermolecular association

Year: 2025

Type: article

Abstract: Murein lipoprotein (Lpp), also known as Braun's lipoprotein, stabilizes the cell wall of Escherichia coli by covalently tethering the outer membrane to the peptidoglycan (PG). Unlike E. coli , Salmonella enterica serovar Typhimurium encodes two murein lipoproteins, LppA and LppB, with LppB bearing an unusual C-terminal sequence, -RICK COOH . Here, we investigated how LppA and LppB bind to the PG. Both lipoproteins were detected in pure PG material in a ~ 400:1 LppA:LppB ratio with some LppB molecules forming a cysteine 78 (C78)-C78 intermolecular disulphide bridge. LppA and LppB anchor covalently to uncross-linked and cross-linked muropeptides. However, unlike LppA, which binds to 4,3- and 3,3-cross-linked muropeptides, LppB shows preferred binding to 4,3-cross-linked muropeptides. Mass spectrometry data revealed O -methylation at the terminal K79 residue in some PG-bound LppB molecules. The apparent selective anchoring of LppB to the PG and the K79 modification require the presence of the C78 residue. Anchoring of LppB to PG is mediated by the L,D-transpeptidase LdtB. A survey in more than 158,000 Salmonella genomes identified up to 31 murein Lpp variants differing in the C-terminal region that cluster in three phylogenetic groups. Most serovars of S. enterica subspecies enterica , responsible for infections in warm blooded animals, encode two or even three murein Lpp variants. Altogether, our data are consistent with subtle differences in the mode that LppB anchors to the PG and uncover an unprecedented diversity of murein lipoproteins within the Salmonella genus. The possibility that this variability evolved as strategy to evade host innate immunity, is also discussed. • Salmonella Typhimurium encodes a murein lipoprotein forming a disulphide bridge. • Salmonella Typhimurium co-expresses two murein lipoproteins, LppA and LppB. • Unlike LppA, LppB does not show anchoring to muropeptides with 3,3-cross-link. • Many Salmonella enterica serovars encode a minimum of two murein lipoproteins. • Multiplicity of murein lipoproteins is notable in Salmonella enterica subspecies I.

Source: The Cell Surface

DOI: 10.1016/j.tcsw.2025.100161

Authors: Marcos Peñalver, Juan J. Cestero, Alberto Paradela, Felipe Cava, Francisco García-del Portillo