TY - JOUR
T1 - C4-dicarboxylates and l-aspartate utilization by Escherichia coli K-12 in the mouse intestine
T2 - l-aspartate as a major substrate for fumarate respiration and as a nitrogen source
AU - Schubert, Christopher
AU - Winter, Maria
AU - Ebert-Jung, Andrea
AU - Kierszniowska, Sylwia
AU - Nagel-Wolfrum, Kerstin
AU - Schramm, Thorben
AU - Link, Hannes
AU - Winter, Sebastian
AU - Unden, Gottfried
N1 - Funding Information:
We are grateful to Deutsche Forschungsgemeinschaft (UN 49/19‐1) for financial support, to S. Wörner (Mainz) for help with some experiments and the National BioResource Project (NIG, Japan) for providing . strains. Work in S.E.W.'s lab was funded by The Welch Foundation (I‐1969‐20180324), NIH (AI118807, AI128151), the Burroughs Wellcome Fund (1017880) and a Research Scholar Grant (RSG‐17‐048‐01‐MPC) from the American Cancer Society. Any opinions, findings, conclusions, or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the funding agencies. The funders had no role in study design, data collection, interpretation, or decision to submit the work for publication. E coli
Publisher Copyright:
© 2021 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.
PY - 2021/5
Y1 - 2021/5
N2 - C4-dicarboxylates, such as fumarate, l-malate and l-aspartate represent substrates for anaerobic growth of Escherichia coli by fumarate respiration. Here, we determined whether C4-dicarboxylate metabolism, as well as fumarate respiration, contribute to colonization of the mammalian intestinal tract. Metabolite profiling revealed that the murine small intestine contained high and low levels of l-aspartate and l-malate respectively, whereas fumarate was nearly absent. Under laboratory conditions, addition of C4-dicarboxylate at concentrations corresponding to the levels of the C4-dicarboxylates in the small intestine (2.6 mmol kg−1 dry weight) induced the dcuBp-lacZ reporter gene (67% of maximal) in a DcuS-DcuR-dependent manner. In addition to its role as a precursor for fumarate respiration, l-aspartate was able to supply all the nitrogen required for anaerobically growing E. coli. DcuS-DcuR-dependent genes were transcribed in the murine intestine, and mutants with defective anaerobic C4-dicarboxylate metabolism (dcuSR, frdA, dcuB, dcuA and aspA genes) were impaired for colonizing the murine gut. We conclude that l-aspartate plays an important role in providing fumarate for fumarate respiration and supplying nitrogen for E. coli in the mouse intestine.
AB - C4-dicarboxylates, such as fumarate, l-malate and l-aspartate represent substrates for anaerobic growth of Escherichia coli by fumarate respiration. Here, we determined whether C4-dicarboxylate metabolism, as well as fumarate respiration, contribute to colonization of the mammalian intestinal tract. Metabolite profiling revealed that the murine small intestine contained high and low levels of l-aspartate and l-malate respectively, whereas fumarate was nearly absent. Under laboratory conditions, addition of C4-dicarboxylate at concentrations corresponding to the levels of the C4-dicarboxylates in the small intestine (2.6 mmol kg−1 dry weight) induced the dcuBp-lacZ reporter gene (67% of maximal) in a DcuS-DcuR-dependent manner. In addition to its role as a precursor for fumarate respiration, l-aspartate was able to supply all the nitrogen required for anaerobically growing E. coli. DcuS-DcuR-dependent genes were transcribed in the murine intestine, and mutants with defective anaerobic C4-dicarboxylate metabolism (dcuSR, frdA, dcuB, dcuA and aspA genes) were impaired for colonizing the murine gut. We conclude that l-aspartate plays an important role in providing fumarate for fumarate respiration and supplying nitrogen for E. coli in the mouse intestine.
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U2 - 10.1111/1462-2920.15478
DO - 10.1111/1462-2920.15478
M3 - Article
C2 - 33754467
AN - SCOPUS:85104262197
VL - 23
SP - 2564
EP - 2577
JO - Environmental Microbiology
JF - Environmental Microbiology
SN - 1462-2912
IS - 5
ER -