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Characterization of inositol lipid metabolism in gut-associated Bacteroidetes

Characterization of inositol lipid metabolism in gut-associated Bacteroidetes

Authors :
Stacey L. Heaver
Henry H. Le
Peijun Tang
Arnaud Baslé
Claudia Mirretta Barone
Dai Long Vu
Jillian L. Waters
Jon Marles-Wright
Elizabeth L. Johnson
Dominic J. Campopiano
Ruth E. Ley
Source :
Heaver, S L, Le, H H, Tang, P, Baslé, A, Mirretta Barone, C, Vu, D L, Waters, J L, Marles-Wright, J, Johnson, E L, Campopiano, D J & Ley, R E 2022, ' Characterization of inositol lipid metabolism in gut-associated Bacteroidetes ', Nature Microbiology, vol. 7, no. 7, pp. 986-1000 . https://doi.org/10.1038/s41564-022-01152-6
Publication Year :
2022
Publisher :
Springer Science and Business Media LLC, 2022.

Abstract

Inositol lipids are ubiquitous in eukaryotes and have finely tuned roles in cellular signalling and membrane homoeostasis. In Bacteria, however, inositol lipid production is relatively rare. Recently, the prominent human gut bacterium Bacteroides thetaiotaomicron (BT) was reported to produce inositol lipids and sphingolipids, but the pathways remain ambiguous and their prevalence unclear. Here, using genomic and biochemical approaches, we investigated the gene cluster for inositol lipid synthesis in BT using a previously undescribed strain with inducible control of sphingolipid synthesis. We characterized the biosynthetic pathway from myo-inositol-phosphate (MIP) synthesis to phosphoinositol dihydroceramide, determined the crystal structure of the recombinant BT MIP synthase enzyme and identified the phosphatase responsible for the conversion of bacterially-derived phosphatidylinositol phosphate (PIP-DAG) to phosphatidylinositol (PI-DAG). In vitro, loss of inositol lipid production altered BT capsule expression and antimicrobial peptide resistance. In vivo, loss of inositol lipids decreased bacterial fitness in a gnotobiotic mouse model. We identified a second putative, previously undescribed pathway for bacterial PI-DAG synthesis without a PIP-DAG intermediate, common in Prevotella. Our results indicate that inositol sphingolipid production is widespread in host-associated Bacteroidetes and has implications for symbiosis.

Details

ISSN :
20585276
Volume :
7
Database :
OpenAIRE
Journal :
Nature Microbiology
Accession number :
edsair.doi.dedup.....3d986f673c77c395aa6380440b1d8264
Full Text :
https://doi.org/10.1038/s41564-022-01152-6