1. Import of Aspartate and Malate by DcuABC Drives H2/Fumarate Respiration to Promote Initial Salmonella Gut-Lumen Colonization in Mice
- Author
-
Rebekka Bauer, Ersin Gül, Beat Christen, V Miguelangel Cuenca, Shinichi Sunagawa, Leanid Laganenka, Franziska Besser, Julia A. Vorholt, Laura Heeb, Steffen Porwollik, Philipp J. Keller, Bidong D. Nguyen, Joel Rüthi, Susanne Meile, Johannes Hartl, Lea Fuchs, Michael McClelland, Pau Pérez Escriva, Wolf-Dietrich Hardt, Matthias Christen, Uwe Sauer, Céline Margot, Céline Fetz, and Markus Furter
- Subjects
Salmonella typhimurium ,Male ,Salmonella ,Antiporter ,Malates ,Succinic Acid ,medicine.disease_cause ,Inbred C57BL ,Feces ,Mice ,0302 clinical medicine ,Fumarates ,Colonization ,chemistry.chemical_classification ,0303 health sciences ,Electron acceptor ,Intestines ,Infectious Diseases ,Medical Microbiology ,Administration ,Female ,Sequence Analysis ,Oral ,16S ,Anaerobic respiration ,mouse model ,Citric Acid Cycle ,Immunology ,Biology ,Microbiology ,03 medical and health sciences ,Metabolism ,Intestine ,Infection ,Mouse model ,Bacterial Proteins ,Virology ,Respiration ,medicine ,Escherichia coli ,Animals ,intestine ,030304 developmental biology ,Ribosomal ,Aspartic Acid ,Animal ,DNA ,infection ,Gastrointestinal Microbiome ,Enzyme ,Emerging Infectious Diseases ,chemistry ,Mutagenesis ,Disease Models ,RNA ,Parasitology ,Digestive Diseases ,metabolism ,030217 neurology & neurosurgery - Abstract
Summary Initial enteropathogen growth in the microbiota-colonized gut is poorly understood. Salmonella Typhimurium is metabolically adaptable and can harvest energy by anaerobic respiration using microbiota-derived hydrogen (H2) 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. Here, transposon sequencing analysis along the colonization trajectory of S. Typhimurium implicates the C4-dicarboxylate antiporter DcuABC in early murine gut colonization. In competitive colonization assays, DcuABC and enzymes that convert the C4-dicarboxylates aspartate and malate into fumarate (AspA, FumABC), are required for fumarate/H2-dependent initial growth. Thus, S. Typhimurium obtains fumarate by DcuABC-mediated import and conversion of L-malate and L-aspartate. Fumarate reduction yields succinate, which is exported by DcuABC in exchange for L-aspartate and L-malate. This cycle allows S. Typhimurium to harvest energy by H2/fumarate respiration in the microbiota-colonized gut. This strategy may also be relevant for commensal E. coli diminishing the S. Typhimurium infection.
- Published
- 2020