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Import of Aspartate and Malate by DcuABC Drives H 2/Fumarate Respiration to Promote Salmonella Gut-Luminal Colonization

68 Pages Posted: 23 Sep 2019 Sneak Peek Status: Review Complete

See all articles by Bidong D. Nguyen

Bidong D. Nguyen

ETH Zürich - Institute of Microbiology

Miguelangel Cuenca V.

ETH Zürich - Institute of Microbiology

Johannes Hartl

ETH Zürich - Institute of Microbiology

Rebekka Bauer

ETH Zürich - Institute of Microbiology

Susanne Meile

ETH Zürich - Institute of Microbiology

Joel Rüthi

ETH Zürich - Institute of Microbiology

Celine Margot

ETH Zürich - Institute of Microbiology

Laura Heeb

ETH Zürich - Institute of Microbiology

Franziska Besser

ETH Zürich - Institute of Microbiology

Pau Perez Escriva

ETH Zürich - Institute of Molecular Systems Biology (IMSB)

Celine Fetz

ETH Zürich - Institute of Microbiology

Markus Furter

ETH Zürich - Institute of Microbiology

Matthias Christen

ETH Zürich - Institute of Molecular Systems Biology (IMSB)

Steffen Porwollik

ETH Zürich - Institute of Molecular Systems Biology (IMSB)

Michael McClelland

University of California, Irvine - Department of Microbiology and Molecular Genetics

Julia A. Vorholt

ETH Zürich - Institute of Microbiology

Uwe Sauer

ETH Zürich - Institute of Molecular Systems Biology (IMSB)

Shinichi Sunagawa

ETH Zürich - Institute of Microbiology

Beat Christen

ETH Zürich - Institute of Molecular Systems Biology (IMSB)

Wolf-Dietrich Hardt

ETH Zürich - Institute of Microbiology

More...

Abstract

Enteropathogen growth in the microbiota-colonized gut is poorly understood. Salmonella Typhimurium is metabolically plastic and can harvest energy by anaerobic respiration using hydrogen (H2), a product of microbiota metabolism, as an electron donor and fumarate as an electron acceptor. As fumarate is scarce in the gut, the source of this electron acceptor is unclear. Transposon sequencing analysis along the colonization-trajectory of S.Typhimurium implicated the C4-dicarboxylate exchanger DcuABC in murine gut colonization. In competitive colonization assays, DcuABC and enzymes converting the C4-dicarboxylates aspartate and malate into fumarate (AspA, FumABC), were required for fumarate/H2-dependent growth. Thus, S.Typhimurium obtains fumarate by DcuABC-mediated import and the subsequent conversion of L-malate and L-aspartate into fumarate. Fumarate reduction yields succinate, which is exported by DcuABC in exchange for L-aspartate and L-malate. This mechanism allows S.Typhimurium to harvest energy by H2/fumarate respiration in the microbiota-colonized gut. It might be relevant for other enteropathogens encoding the requisite genes.

Keywords: Salmonella, metabolism, intestine, infection, mouse model

Suggested Citation

Nguyen, Bidong D. and Cuenca V., Miguelangel and Hartl, Johannes and Bauer, Rebekka and Meile, Susanne and Rüthi, Joel and Margot, Celine and Heeb, Laura and Besser, Franziska and Perez Escriva, Pau and Fetz, Celine and Furter, Markus and Christen, Matthias and Porwollik, Steffen and McClelland, Michael and Vorholt, Julia A. and Sauer, Uwe and Sunagawa, Shinichi and Christen, Beat and Hardt, Wolf-Dietrich, Import of Aspartate and Malate by DcuABC Drives H 2/Fumarate Respiration to Promote Salmonella Gut-Luminal Colonization (September 20, 2019). Available at SSRN: https://ssrn.com/abstract=3456942 or http://dx.doi.org/10.2139/ssrn.3456942
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Bidong D. Nguyen

ETH Zürich - Institute of Microbiology

Switzerland

Miguelangel Cuenca V.

ETH Zürich - Institute of Microbiology

Switzerland

Johannes Hartl

ETH Zürich - Institute of Microbiology

Switzerland

Rebekka Bauer

ETH Zürich - Institute of Microbiology

Switzerland

Susanne Meile

ETH Zürich - Institute of Microbiology

Switzerland

Joel Rüthi

ETH Zürich - Institute of Microbiology

Switzerland

Celine Margot

ETH Zürich - Institute of Microbiology

Switzerland

Laura Heeb

ETH Zürich - Institute of Microbiology

Switzerland

Franziska Besser

ETH Zürich - Institute of Microbiology

Switzerland

Pau Perez Escriva

ETH Zürich - Institute of Molecular Systems Biology (IMSB)

Building HPT
Auguste-Piccard-Hof 1
Zürich, 8093
Switzerland

Celine Fetz

ETH Zürich - Institute of Microbiology

Switzerland

Markus Furter

ETH Zürich - Institute of Microbiology

Switzerland

Matthias Christen

ETH Zürich - Institute of Molecular Systems Biology (IMSB)

Building HPT
Auguste-Piccard-Hof 1
Zürich, 8093
Switzerland

Steffen Porwollik

ETH Zürich - Institute of Molecular Systems Biology (IMSB)

Building HPT
Auguste-Piccard-Hof 1
Zürich, 8093
Switzerland

Michael McClelland

University of California, Irvine - Department of Microbiology and Molecular Genetics

United States

Julia A. Vorholt

ETH Zürich - Institute of Microbiology

Switzerland

Uwe Sauer

ETH Zürich - Institute of Molecular Systems Biology (IMSB)

Building HPT
Auguste-Piccard-Hof 1
Zürich, 8093
Switzerland

Shinichi Sunagawa

ETH Zürich - Institute of Microbiology

Switzerland

Beat Christen

ETH Zürich - Institute of Molecular Systems Biology (IMSB)

Building HPT
Auguste-Piccard-Hof 1
Zürich, 8093
Switzerland

Wolf-Dietrich Hardt (Contact Author)

ETH Zürich - Institute of Microbiology ( email )

Switzerland

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