Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria

The Journal of Experimental Medicine
Peter ReininkIldiko Van Rhijn

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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Citations

Aug 31, 2020·Virulence·Muthita Vanaporn, Richard W Titball
Sep 12, 2020·Chemical Communications : Chem Comm·Karishma KaleraBenjamin M Swarts
Mar 3, 2019·The Journal of Experimental Medicine·Stephanie R Lovell-Read, Luiz Pedro Sorio de Carvalho
Dec 5, 2020·ACS Central Science·Yamuna KrishnanMaulik S Jani
Apr 25, 2021·The Journal of Biological Chemistry·Marten ExterkateArnold J M Driessen

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Methods Mentioned

BETA
nuclear magnetic resonance
scrapings
NMR
gene knockouts
gene knockout
PCR

Software Mentioned

trimAl
BLASTP
R package drc
SILVA
iqtree
MS n
MrBayes
BLAST
diPT
XCMS

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