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Emerging knowledge of regulatory roles of D-amino acids in bacteria.

Cava F, Lam H, de Pedro MA, Waldor MK - Cell. Mol. Life Sci. (2010)

Bottom Line: Many diverse bacterial phyla synthesize and release D-amino acids, including D-Met and D-Leu, which were not previously known to be made.These noncanonical D-amino acids regulate cell wall remodeling in stationary phase and cause biofilm dispersal in aging bacterial communities.Elucidating the mechanisms by which D-amino acids govern cell wall remodeling and biofilm disassembly will undoubtedly reveal new paradigms for understanding how extracytoplasmic processes are regulated as well as lead to development of novel therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA 02115, USA. fcava@rics.bwh.harvard.edu

ABSTRACT
The D-enantiomers of amino acids have been thought to have relatively minor functions in biological processes. While L-amino acids clearly predominate in nature, D-amino acids are sometimes found in proteins that are not synthesized by ribosomes, and D-Ala and D-Glu are routinely found in the peptidoglycan cell wall of bacteria. Here, we review recent findings showing that D-amino acids have previously unappreciated regulatory roles in the bacterial kingdom. Many diverse bacterial phyla synthesize and release D-amino acids, including D-Met and D-Leu, which were not previously known to be made. These noncanonical D-amino acids regulate cell wall remodeling in stationary phase and cause biofilm dispersal in aging bacterial communities. Elucidating the mechanisms by which D-amino acids govern cell wall remodeling and biofilm disassembly will undoubtedly reveal new paradigms for understanding how extracytoplasmic processes are regulated as well as lead to development of novel therapeutics.

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Biosynthesis of peptidoglycan (PG). General scheme of PG synthesis in gram negative bacteria. PG synthesis is initiated with the synthesis of the disaccharide pentapeptide precursors in the cytosol (GlcNAc-MurNAc-l-Ala-d-Glu-DAP-d-Ala-d-Ala) [42]. Then, PG precursors are translocated to the periplasmic space facilitated by the formation of lipidic complexes with bactoprenol [43, 44]. Once in the periplasm, PG monomers are incorporated into the murein polymer by transglycosylation and transpeptidation reactions carried out by the activity of the penicillin-binding proteins (PBPs) [45–48]. Also PBP activities (murein hydrolases) can affect the length of the stem peptides, depicted as d-Ala between brackets [43]. IM Inner membrane, OM outer membrane
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Fig2: Biosynthesis of peptidoglycan (PG). General scheme of PG synthesis in gram negative bacteria. PG synthesis is initiated with the synthesis of the disaccharide pentapeptide precursors in the cytosol (GlcNAc-MurNAc-l-Ala-d-Glu-DAP-d-Ala-d-Ala) [42]. Then, PG precursors are translocated to the periplasmic space facilitated by the formation of lipidic complexes with bactoprenol [43, 44]. Once in the periplasm, PG monomers are incorporated into the murein polymer by transglycosylation and transpeptidation reactions carried out by the activity of the penicillin-binding proteins (PBPs) [45–48]. Also PBP activities (murein hydrolases) can affect the length of the stem peptides, depicted as d-Ala between brackets [43]. IM Inner membrane, OM outer membrane

Mentions: Bacteria have a formidable ability to withstand many physical, chemical, and biological insults. In large part, this is due to the peptidoglycan (PG) cell wall, which imparts to the cell its shape, strength, and resistance to osmotic pressure [36–38]. PG also serves as a scaffold for anchoring other cell envelope components [39, 40]. PG (also known as murein) is found on the outside of the cytoplasmic membrane of almost all bacteria [36, 41, 42]. It is a strong yet flexible net-like polymer composed of linear glycan strands made up of repeating disaccharide units of N-acetyl glucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) cross-linked by short peptides (Fig. 2). PG is essential for cell viability and therefore its synthesis and turnover must be tightly controlled; otherwise, the mechanical stability of the cell wall and cell integrity would be compromised. In gram-negative bacteria, a single layer of PG, which is found in the periplasmic space between the inner and outer cell membranes, is sufficient to maintain the cell’s mechanical stability [43]. In gram-positive bacteria, which lack an outer cell membrane, the cell wall is thicker, consisting of many layers of PG.Fig. 2


Emerging knowledge of regulatory roles of D-amino acids in bacteria.

Cava F, Lam H, de Pedro MA, Waldor MK - Cell. Mol. Life Sci. (2010)

Biosynthesis of peptidoglycan (PG). General scheme of PG synthesis in gram negative bacteria. PG synthesis is initiated with the synthesis of the disaccharide pentapeptide precursors in the cytosol (GlcNAc-MurNAc-l-Ala-d-Glu-DAP-d-Ala-d-Ala) [42]. Then, PG precursors are translocated to the periplasmic space facilitated by the formation of lipidic complexes with bactoprenol [43, 44]. Once in the periplasm, PG monomers are incorporated into the murein polymer by transglycosylation and transpeptidation reactions carried out by the activity of the penicillin-binding proteins (PBPs) [45–48]. Also PBP activities (murein hydrolases) can affect the length of the stem peptides, depicted as d-Ala between brackets [43]. IM Inner membrane, OM outer membrane
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3037491&req=5

Fig2: Biosynthesis of peptidoglycan (PG). General scheme of PG synthesis in gram negative bacteria. PG synthesis is initiated with the synthesis of the disaccharide pentapeptide precursors in the cytosol (GlcNAc-MurNAc-l-Ala-d-Glu-DAP-d-Ala-d-Ala) [42]. Then, PG precursors are translocated to the periplasmic space facilitated by the formation of lipidic complexes with bactoprenol [43, 44]. Once in the periplasm, PG monomers are incorporated into the murein polymer by transglycosylation and transpeptidation reactions carried out by the activity of the penicillin-binding proteins (PBPs) [45–48]. Also PBP activities (murein hydrolases) can affect the length of the stem peptides, depicted as d-Ala between brackets [43]. IM Inner membrane, OM outer membrane
Mentions: Bacteria have a formidable ability to withstand many physical, chemical, and biological insults. In large part, this is due to the peptidoglycan (PG) cell wall, which imparts to the cell its shape, strength, and resistance to osmotic pressure [36–38]. PG also serves as a scaffold for anchoring other cell envelope components [39, 40]. PG (also known as murein) is found on the outside of the cytoplasmic membrane of almost all bacteria [36, 41, 42]. It is a strong yet flexible net-like polymer composed of linear glycan strands made up of repeating disaccharide units of N-acetyl glucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) cross-linked by short peptides (Fig. 2). PG is essential for cell viability and therefore its synthesis and turnover must be tightly controlled; otherwise, the mechanical stability of the cell wall and cell integrity would be compromised. In gram-negative bacteria, a single layer of PG, which is found in the periplasmic space between the inner and outer cell membranes, is sufficient to maintain the cell’s mechanical stability [43]. In gram-positive bacteria, which lack an outer cell membrane, the cell wall is thicker, consisting of many layers of PG.Fig. 2

Bottom Line: Many diverse bacterial phyla synthesize and release D-amino acids, including D-Met and D-Leu, which were not previously known to be made.These noncanonical D-amino acids regulate cell wall remodeling in stationary phase and cause biofilm dispersal in aging bacterial communities.Elucidating the mechanisms by which D-amino acids govern cell wall remodeling and biofilm disassembly will undoubtedly reveal new paradigms for understanding how extracytoplasmic processes are regulated as well as lead to development of novel therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA 02115, USA. fcava@rics.bwh.harvard.edu

ABSTRACT
The D-enantiomers of amino acids have been thought to have relatively minor functions in biological processes. While L-amino acids clearly predominate in nature, D-amino acids are sometimes found in proteins that are not synthesized by ribosomes, and D-Ala and D-Glu are routinely found in the peptidoglycan cell wall of bacteria. Here, we review recent findings showing that D-amino acids have previously unappreciated regulatory roles in the bacterial kingdom. Many diverse bacterial phyla synthesize and release D-amino acids, including D-Met and D-Leu, which were not previously known to be made. These noncanonical D-amino acids regulate cell wall remodeling in stationary phase and cause biofilm dispersal in aging bacterial communities. Elucidating the mechanisms by which D-amino acids govern cell wall remodeling and biofilm disassembly will undoubtedly reveal new paradigms for understanding how extracytoplasmic processes are regulated as well as lead to development of novel therapeutics.

Show MeSH
Related in: MedlinePlus