Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 325 (5947): 1552-1555

Copyright © 2009 by the American Association for the Advancement of Science

D-Amino Acids Govern Stationary Phase Cell Wall Remodeling in Bacteria

Hubert Lam,1,* Dong-Chan Oh,2,*,{dagger} Felipe Cava,1,* Constantin N. Takacs,1,{ddagger} Jon Clardy,2 Miguel A. de Pedro,3 Matthew K. Waldor1,§

Abstract: In all known organisms, amino acids are predominantly thought to be synthesized and used as their L-enantiomers. Here, we found that bacteria produce diverse D-amino acids as well, which accumulate at millimolar concentrations in supernatants of stationary phase cultures. In Vibrio cholerae, a dedicated racemase produced D-Met and D-Leu, whereas Bacillus subtilis generated D-Tyr and D-Phe. These unusual D-amino acids appear to modulate synthesis of peptidoglycan, a strong and elastic polymer that serves as the stress-bearing component of the bacterial cell wall. D-Amino acids influenced peptidoglycan composition, amount, and strength, both by means of their incorporation into the polymer and by regulating enzymes that synthesize and modify it. Thus, synthesis of D-amino acids may be a common strategy for bacteria to adapt to changing environmental conditions.

1 Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA 02115, USA.
2 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
3 Centro de Biología Molecular "Severo Ochoa" Consejo Superior de Investigaciones, Científicas-Universidad Autónoma de Madrid, Facultad de Ciencias, 28049 Madrid, Spain.

* These authors contributed equally to this work.

{dagger} Present address: Natural Products Research Institute, College of Pharmacy, Seoul National University, San 56-1, Sillim, Seoul 151-742, Republic of Korea.

{ddagger} Present address: Yale University, New Haven, CT 06520, USA.

§ To whom correspondence should be addressed. E-mail: mwaldor{at}rics.bwh.harvard.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Differential Requirement for PBP1a and PBP1b in In Vivo and In Vitro Fitness of Vibrio cholerae.
T. Dorr, A. Moll, M. C. Chao, F. Cava, H. Lam, B. M. Davis, and M. K. Waldor (2014)
Infect. Immun. 82, 2115-2124
   Abstract »    Full Text »    PDF »
Function and Localization Dynamics of Bifunctional Penicillin-Binding Proteins in Caulobacter crescentus.
W. Strobel, A. Moll, D. Kiekebusch, K. E. Klein, and M. Thanbichler (2014)
J. Bacteriol. 196, 1627-1639
   Abstract »    Full Text »    PDF »
Imaging bacterial peptidoglycan with near-infrared fluorogenic azide probes.
P. Shieh, M. S. Siegrist, A. J. Cullen, and C. R. Bertozzi (2014)
PNAS 111, 5456-5461
   Abstract »    Full Text »    PDF »
Streptococcus pneumoniae detects and responds to foreign bacterial peptide fragments in its environment.
L. J. Hathaway, P. Battig, S. Reber, J. U. Rotzetter, S. Aebi, C. Hauser, M. Heller, A. Kadioglu, and K. Muhlemann (2014)
Open Bio 4, 130224
   Abstract »    Full Text »    PDF »
Amino Acid Racemization in Pseudomonas putida KT2440.
A. D. Radkov and L. A. Moe (2013)
J. Bacteriol. 195, 5016-5024
   Abstract »    Full Text »    PDF »
Identification, Purification, and Characterization of a Novel Amino Acid Racemase, Isoleucine 2-Epimerase, from Lactobacillus Species.
Y. Mutaguchi, T. Ohmori, T. Wakamatsu, K. Doi, and T. Ohshima (2013)
J. Bacteriol. 195, 5207-5215
   Abstract »    Full Text »    PDF »
Amino acids in the rhizosphere: From plants to microbes.
L. A. Moe (2013)
Am. J. Botany 100, 1692-1705
   Abstract »    Full Text »    PDF »
Bacterial Biofilms: Development, Dispersal, and Therapeutic Strategies in the Dawn of the Postantibiotic Era.
M. Kostakioti, M. Hadjifrangiskou, and S. J. Hultgren (2013)
Cold Spring Harb Perspect Med 3, a010306
   Abstract »    Full Text »    PDF »
Extensive Reduction of Cell Viability and Enhanced Matrix Production in Pseudomonas aeruginosa PAO1 Flow Biofilms Treated with a D-Amino Acid Mixture.
Z. Sanchez, A. Tani, and K. Kimbara (2013)
Appl. Envir. Microbiol. 79, 1396-1399
   Abstract »    Full Text »    PDF »
A Trapping Approach Reveals Novel Substrates and Physiological Functions of the Essential Protease FtsH in Escherichia coli.
K. Westphal, S. Langklotz, N. Thomanek, and F. Narberhaus (2012)
J. Biol. Chem. 287, 42962-42971
   Abstract »    Full Text »    PDF »
Functional amyloid formation by Streptococcus mutans.
M. W. Oli, H. N. Otoo, P. J. Crowley, K. P. Heim, M. M. Nascimento, C. B. Ramsook, P. N. Lipke, and L. J. Brady (2012)
Microbiology 158, 2903-2916
   Abstract »    Full Text »    PDF »
Fresh Approaches to Anti-Infective Therapies.
C. Nathan (2012)
Science Translational Medicine 4, 140sr2
   Full Text »    PDF »
Protective Role of D-Amino Acid Oxidase against Staphylococcus aureus Infection.
H. Nakamura, J. Fang, and H. Maeda (2012)
Infect. Immun. 80, 1546-1553
   Abstract »    Full Text »    PDF »
Inhibitory Effects of D-Amino Acids on Staphylococcus aureus Biofilm Development.
A. I. Hochbaum, I. Kolodkin-Gal, L. Foulston, R. Kolter, J. Aizenberg, and R. Losick (2011)
J. Bacteriol. 193, 5616-5622
   Abstract »    Full Text »    PDF »
Distinct pathways for modification of the bacterial cell wall by non-canonical D-amino acids.
F. Cava, M. A. de Pedro, H. Lam, B. M. Davis, and M. K. Waldor (2011)
EMBO J. 30, 3442-3453
   Abstract »    Full Text »    PDF »
Intestine may be a major site of action for the apoA-I mimetic peptide 4F whether administered subcutaneously or orally.
M. Navab, S. T. Reddy, G. M. Anantharamaiah, S. Imaizumi, G. Hough, S. Hama, and A. M. Fogelman (2011)
J. Lipid Res. 52, 1200-1210
   Abstract »    Full Text »    PDF »
Regulation and Characterization of the dadRAX Locus for D-Amino Acid Catabolism in Pseudomonas aeruginosa PAO1.
W. He, C. Li, and C.-D. Lu (2011)
J. Bacteriol. 193, 2107-2115
   Abstract »    Full Text »    PDF »
A Role for the Class A Penicillin-Binding Protein PonA2 in the Survival of Mycobacterium smegmatis under Conditions of Nonreplication.
M.-M. Patru and M. S. Pavelka Jr. (2010)
J. Bacteriol. 192, 3043-3054
   Abstract »    Full Text »    PDF »
D-Amino Acids Trigger Biofilm Disassembly.
I. Kolodkin-Gal, D. Romero, S. Cao, J. Clardy, R. Kolter, and R. Losick (2010)
Science 328, 627-629
   Abstract »    Full Text »    PDF »
Global Regulation of Food Supply by Pseudomonas putida DOT-T1E.
C. Daniels, P. Godoy, E. Duque, M. A. Molina-Henares, J. de la Torre, J. M. del Arco, C. Herrera, A. Segura, M. E. Guazzaroni, M. Ferrer, et al. (2010)
J. Bacteriol. 192, 2169-2181
   Abstract »    Full Text »    PDF »
Expanding Functionality Within the Looking-Glass Universe.
S. R. Blanke (2009)
Science 325, 1505-1506
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882