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Abstract:
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.
