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Lactate racemization as a rescue pathway for supplying D-lactate to the cell wall biosynthesis machinery in Lactobacillus plantarum.
- Source :
-
Journal of bacteriology [J Bacteriol] 2005 Oct; Vol. 187 (19), pp. 6750-61. - Publication Year :
- 2005
-
Abstract
- Lactobacillus plantarum is a lactic acid bacterium that produces d- and l-lactate using stereospecific NAD-dependent lactate dehydrogenases (LdhD and LdhL, respectively). However, reduction of glycolytic pyruvate by LdhD is not the only pathway for d-lactate production since a mutant defective in this activity still produces both lactate isomers (T. Ferain, J. N. Hobbs, Jr., J. Richardson, N. Bernard, D. Garmyn, P. Hols, N. E. Allen, and J. Delcour, J. Bacteriol. 178:5431-5437, 1996). Production of d-lactate in this species has been shown to be connected to cell wall biosynthesis through its incorporation as the last residue of the muramoyl-pentadepsipeptide peptidoglycan precursor. This particular feature leads to natural resistance to high concentrations of vancomycin. In the present study, we show that L. plantarum possesses two pathways for d-lactate production: the LdhD enzyme and a lactate racemase, whose expression requires l-lactate. We report the cloning of a six-gene operon, which is involved in lactate racemization activity and is positively regulated by l-lactate. Deletion of this operon in an L. plantarum strain that is devoid of LdhD activity leads to the exclusive production of l-lactate. As a consequence, peptidoglycan biosynthesis is affected, and growth of this mutant is d-lactate dependent. We also show that the growth defect can be partially restored by expression of the d-alanyl-d-alanine-forming Ddl ligase from Lactococcus lactis, or by supplementation with various d-2-hydroxy acids but not d-2-amino acids, leading to variable vancomycin resistance levels. This suggests that L. plantarum is unable to efficiently synthesize peptidoglycan precursors ending in d-alanine and that the cell wall biosynthesis machinery in this species is specifically dedicated to the production of peptidoglycan precursors ending in d-lactate. In this context, the lactate racemase could thus provide the bacterium with a rescue pathway for d-lactate production upon inactivation or inhibition of the LdhD enzyme.
- Subjects :
- Amino Acids metabolism
Cell Wall metabolism
Cloning, Molecular
Hydroxy Acids metabolism
L-Lactate Dehydrogenase genetics
L-Lactate Dehydrogenase metabolism
Lactate Dehydrogenases metabolism
Lactates chemistry
Lactobacillus plantarum genetics
Mutation
Operon physiology
Peptide Synthases metabolism
Peptidoglycan biosynthesis
Peptidoglycan metabolism
Racemases and Epimerases biosynthesis
Lactates metabolism
Lactobacillus plantarum enzymology
Racemases and Epimerases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9193
- Volume :
- 187
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Journal of bacteriology
- Publication Type :
- Academic Journal
- Accession number :
- 16166538
- Full Text :
- https://doi.org/10.1128/JB.187.19.6750-6761.2005