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Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria.

Published version
Peer-reviewed

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Article

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Abstract

Salmonella species are among the world's most prevalent pathogens. Because the cell wall interfaces with the host, we designed a lipidomics approach to reveal pathogen-specific cell wall compounds. Among the molecules differentially expressed between Salmonella Paratyphi and S. Typhi, we focused on lipids that are enriched in S. Typhi, because it causes typhoid fever. We discovered a previously unknown family of trehalose phospholipids, 6,6'-diphosphatidyltrehalose (diPT) and 6-phosphatidyltrehalose (PT). Cardiolipin synthase B (ClsB) is essential for PT and diPT but not for cardiolipin biosynthesis. Chemotyping outperformed clsB homology analysis in evaluating synthesis of diPT. DiPT is restricted to a subset of Gram-negative bacteria: large amounts are produced by S. Typhi, lower amounts by other pathogens, and variable amounts by Escherichia coli strains. DiPT activates Mincle, a macrophage activating receptor that also recognizes mycobacterial cord factor (6,6'-trehalose dimycolate). Thus, Gram-negative bacteria show convergent function with mycobacteria. Overall, we discovered a previously unknown immunostimulant that is selectively expressed among medically important bacterial species.

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Keywords

Animals, Cell Membrane, Escherichia coli, Feces, Humans, Lectins, C-Type, Membrane Proteins, Mice, Mycobacterium, Phospholipids, Phylogeny, Receptors, Immunologic, Salmonella typhi, Transferases (Other Substituted Phosphate Groups), Trehalose, Typhoid Fever

Journal Title

J Exp Med

Conference Name

Journal ISSN

0022-1007
1540-9538

Volume Title

216

Publisher

Rockefeller University Press