Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria

Peter Reijnink (First author), Jeffrey Buter (First author), Vivek Mishra, Eri Ishikawa, Tan-Yun Cheng, Peter Willemsen, Steffen Porwollik, Patrick Brennan, Eva Heinz, Jacob Mayfield, Gordon Dougan, Cécile van Els, Vincenzo Cerundolo, Giorgio Napolitani, Sho Yamazaki, Adriaan Minnaard, Michael McClelland, Branch Moody, Ildiko van Rhijn

Research output: Contribution to journalArticleAcademicpeer-review


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
JournalJournal or Experimental Medicine
Issue number4
Publication statusPublished - 25 Feb 2019
Externally publishedYes


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