Listeria monocytogenes growing in complex media (e.g., BHI) catabolizes first glucose (and the other PTS sugars, which are all ultimately converted to glucose-6-phosphate) mainly by the glycolytic pathway. The principal glycolysis genes (gap, pgk, tpi, pgm, and eno) of L. monocytogenes as in most low G+C Gp bacteria belong to the predicted highly expressed genes (Karlin et al., 2004). In glucose-containing minimal medium, these genes are, however, down-regulated and genes of the pentose phosphate pathway (PPP) are induced when compared to BHI (Joseph et al., 2006), indicating the need of the oxidative decarboxylation of glucose by glucose-6-phosphate dehydrogenase (possibly for the production of CO2—see below) and/or the generation of increased amounts of erythrose-4-phophate (for the biosynthesis of aromatic amino acids which are not present in the minimal medium). Interestingly, a similar down-regulation of most glycolysis genes and up-regulation of PPP genes are also observed when L. monocytogenes grows in the cytosol of mammalian host cells (Joseph et al., 2006).
Entry of pyruvate into the citrate cycle affords the oxidative decarboxylation to acetyl-CoA by the lipoate-dependent pyruvate—dehydrogenase; this step seems to be critical for intracellular L. monocytogenes, since a mutant defective in the lipoate ligase 1 (LplAl) is strongly impaired in intracellular growth (O'Riordan et al., 2003).
The citrate cycle of L. monocytogenes is interrupted due to the lack of 2-oxoglutarate dehydrogenase (Eisenreich et al., 2006; Trivett and Meyer, 1971). Hence oxaloacetate, which is essential for the entry of acetyl-CoA into the "cycle" leading to citrate and an important intermediate for the synthesis of Asp and other amino acids belonging to the Asp family, cannot be regenerated from citrate, and its synthesis becomes a crucial step in L. monocyto-genes metabolism. As recently shown by 13C-isotopolog perturbation studies with uniformly labeled 13[C]glucose (Eisenreich et al., 2006), oxaloacetate is mainly produced by carboxylation of pyruvate catalyzed by pyruvate carboxylase (determined by pycA, while a gene for PEP-carboxylase seems to be missing in L. monocytogenes). Oxaloacetate is probably converted into malonate and succinate by the reducing branch of the citrate cycle for the generation of these important intermediates. Thus, for the generation of oxaloacetate by pyruvate carboxylase, CO2 is an essential substrate, and we suggest that the observed induced oxidative decarboxylation of glucose-6-phosphate (first step in the PPP) may be therefore required for growth of L. monocytogenes in glucose-containing minimal medium. The special role of CO2 for growth of L. monocy-togenes and Yersinia pseudotuberculosis was pointed out earlier (Buzolyova and
Somov, 1999). This CO2 requirement may also explain the inability of L. monocytogenes to grow in minimal media with pentoses like ribose or rhamnose as carbon sources, although fermentation of rhamnose is observed in rich media (Groves and Welshimer, 1977).
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