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, Cécile A. van Els, Vincenzo Cerundolo, Giorgio Napolitani, Sho Yamasaki, Adriaan J. Minnaard, Michael McClelland, D.B. Moody, Ildiko Van Rhijn

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

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.

LanguageEnglish
Pages757-771
Number of pages15
JournalThe Journal of experimental medicine
Volume216
Issue number4
DOIs
Publication statusPublished - 1 Apr 2019

Fingerprint

Cord Factors
Trehalose
Mycobacterium
Gram-Negative Bacteria
Salmonella
Cell Wall
Phospholipids
Salmonella paratyphi A
Immunologic Adjuvants
Cardiolipins
Typhoid Fever
Macrophages
Escherichia coli
Lipids

Cite this

Reinink, Peter ; Buter, Jeffrey ; Mishra, Vivek K. ; Ishikawa, Eri ; Cheng, Tan Yun ; Willemsen, Peter T.J. ; Porwollik, Steffen ; Brennan, Patrick J. ; Heinz, Eva ; Mayfield, Jacob A. ; Dougan, Gordon ; van Els, Cécile A. ; Cerundolo, Vincenzo ; Napolitani, Giorgio ; Yamasaki, Sho ; Minnaard, Adriaan J. ; McClelland, Michael ; Moody, D.B. ; Van Rhijn, Ildiko. / Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria. In: The Journal of experimental medicine. 2019 ; Vol. 216, No. 4. pp. 757-771.
@article{5b46b3092a7d43fa839a0dc07d2968d8,
title = "Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria",
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.",
author = "Peter Reinink and Jeffrey Buter and Mishra, {Vivek K.} and Eri Ishikawa and Cheng, {Tan Yun} and Willemsen, {Peter T.J.} and Steffen Porwollik and Brennan, {Patrick J.} and Eva Heinz and Mayfield, {Jacob A.} and Gordon Dougan and {van Els}, {C{\'e}cile A.} and Vincenzo Cerundolo and Giorgio Napolitani and Sho Yamasaki and Minnaard, {Adriaan J.} and Michael McClelland and D.B. Moody and {Van Rhijn}, Ildiko",
year = "2019",
month = "4",
day = "1",
doi = "10.1084/jem.20181812",
language = "English",
volume = "216",
pages = "757--771",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "4",

}

Reinink, P, Buter, J, Mishra, VK, Ishikawa, E, Cheng, TY, Willemsen, PTJ, Porwollik, S, Brennan, PJ, Heinz, E, Mayfield, JA, Dougan, G, van Els, CA, Cerundolo, V, Napolitani, G, Yamasaki, S, Minnaard, AJ, McClelland, M, Moody, DB & Van Rhijn, I 2019, 'Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria', The Journal of experimental medicine, vol. 216, no. 4, pp. 757-771. https://doi.org/10.1084/jem.20181812

Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria. / Reinink, Peter; Buter, Jeffrey; Mishra, Vivek K.; Ishikawa, Eri; Cheng, Tan Yun; Willemsen, Peter T.J.; Porwollik, Steffen; Brennan, Patrick J.; Heinz, Eva; Mayfield, Jacob A.; Dougan, Gordon; van Els, Cécile A.; Cerundolo, Vincenzo; Napolitani, Giorgio; Yamasaki, Sho; Minnaard, Adriaan J.; McClelland, Michael; Moody, D.B.; Van Rhijn, Ildiko.

In: The Journal of experimental medicine, Vol. 216, No. 4, 01.04.2019, p. 757-771.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria

AU - Reinink, Peter

AU - Buter, Jeffrey

AU - Mishra, Vivek K.

AU - Ishikawa, Eri

AU - Cheng, Tan Yun

AU - Willemsen, Peter T.J.

AU - Porwollik, Steffen

AU - Brennan, Patrick J.

AU - Heinz, Eva

AU - Mayfield, Jacob A.

AU - Dougan, Gordon

AU - van Els, Cécile A.

AU - Cerundolo, Vincenzo

AU - Napolitani, Giorgio

AU - Yamasaki, Sho

AU - Minnaard, Adriaan J.

AU - McClelland, Michael

AU - Moody, D.B.

AU - Van Rhijn, Ildiko

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

U2 - 10.1084/jem.20181812

DO - 10.1084/jem.20181812

M3 - Article

VL - 216

SP - 757

EP - 771

JO - Journal of Experimental Medicine

T2 - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 4

ER -