Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria

Peter Reinink, Jeffrey Buter, Vivek K. Mishra, Eri Ishikawa, Tan-Yun Cheng, Peter T. J. Willemsen, Steffen Porwollik, Patrick J. Brennan, Eva Heinz, Jacob A. Mayfield, Gordon Dougan, Cecile A. van Els, Vincenzo Cerundolo, Giorgio Napolitani, Sho Yamasaki, Adriaan J. Minnaard, Michael McCeland, D. Branch Moody, Ildiko Van Rhijn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)757-771
Number of pages15
JournalJournal of Experimental Medicine
Volume216
Issue number4
DOIs
Publication statusPublished - Apr-2019

Keywords

  • CORD FACTOR
  • DIHYDROSTERCULIC ACID
  • LACTOBACILLIC ACID
  • T-CELLS
  • IN-VIVO
  • TUBERCULOSIS
  • RECOGNITION
  • EFFICIENT
  • ALIGNMENT
  • MINCLE

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