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Updated: Jan 28, 2026

Electroporation of Mycobacteria
Published on: May 23, 2008
Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria
Peter Reinink1,2, Jeffrey Buter2, Vivek K Mishra3
1Department of Infectious Diseases and Immunology, School of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
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.
Insights
Researchers discovered a new immunostimulant, 6,6'-diphosphatidyltrehalose (diPT), in *Salmonella* Typhi. This molecule, produced by some Gram-negative bacteria, activates immune cells similarly to mycobacteria.
Area of Science:
- Microbiology
- Immunology
- Lipidomics
Background:
- *Salmonella* species are significant global pathogens.
- The bacterial cell wall is a key interface with host immune systems.
- Understanding pathogen-specific cell wall components can reveal virulence factors and therapeutic targets.
Purpose of the Study:
- To identify novel pathogen-specific cell wall lipids in *Salmonella* species.
- To investigate the role of these lipids in host immune activation.
- To characterize the biosynthesis and distribution of a newly discovered lipid.
Main Methods:
- Lipidomics analysis to compare lipid profiles of *Salmonella* Paratyphi and *S. *Typhi.
- Biochemical assays to determine the function of identified lipids and their biosynthetic pathways.
- Chemotype analysis and gene homology studies to assess lipid synthesis.
Main Results:
- Discovery of a new family of trehalose phospholipids: 6,6 '-diphosphatidyltrehalose (diPT) and 6-phosphatidyltrehalose (PT).
- Cardiolipin synthase B (ClsB) was found to be essential for diPT and PT biosynthesis.
- diPT was identified as an immunostimulant activating the Mincle receptor, similar to mycobacterial cord factor.
Conclusions:
- diPT is a novel immunostimulant selectively produced by a subset of Gram-negative bacteria, including *S. *Typhi.
- The discovery of diPT reveals functional convergence between Gram-negative bacteria and mycobacteria in immune activation.
- This finding opens new avenues for understanding bacterial pathogenesis and developing targeted therapies.
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