Assembling of the Mycobacterium tuberculosis Cell Wall Core*

  1. Mary Jackson‡24
  1. From the ‡Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado 80523-1682,
  2. the §Institute for Integrative Biology of the Cell (I2BC), Commissariat à l'Energie Atomique (CEA), CNRS, Université Paris Sud, F-91198 Gif-sur-Yvette, France,
  3. the Department of Chemistry and Biochemistry, University of Toledo, Toledo, Ohio 43606-3390,
  4. the ‖Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina CH-1, 84215 Bratislava, Slovakia,
  5. the **Key Laboratory of Medical Molecular Virology of MOE & MOH, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China,
  6. the ‡‡Institute of Microbial Chemistry (BIKAKEN), Kamiosaki, Shinagawa-ku, Tokyo 3-14-23, Japan, and
  7. the §§C-CINA Center for Imaging and NanoAnalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland
  1. ↵3 To whom correspondence may be addressed: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris Sud, F-91198 Gif-sur-Yvette, France. E-mail: christine.houssin{at}u-psud.fr.
  2. ↵4 To whom correspondence may be addressed: Dept. of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523-1682. Tel.: 970-491-3582; Fax: 970-491-1815; E-mail: Mary.Jackson{at}colostate.edu.

  1. ↵1 Both authors contributed equally to the work.

Abstract

The unique cell wall of mycobacteria is essential to their viability and the target of many clinically used anti-tuberculosis drugs and inhibitors under development. Despite intensive efforts to identify the ligase(s) responsible for the covalent attachment of the two major heteropolysaccharides of the mycobacterial cell wall, arabinogalactan (AG) and peptidoglycan (PG), the enzyme or enzymes responsible have remained elusive. We here report on the identification of the two enzymes of Mycobacterium tuberculosis, CpsA1 (Rv3267) and CpsA2 (Rv3484), responsible for this function. CpsA1 and CpsA2 belong to the widespread LytR-Cps2A-Psr (LCP) family of enzymes that has been shown to catalyze a variety of glycopolymer transfer reactions in Gram-positive bacteria, including the attachment of wall teichoic acids to PG. Although individual cpsA1 and cpsA2 knock-outs of M. tuberculosis were readily obtained, the combined inactivation of both genes appears to be lethal. In the closely related microorganism Corynebacterium glutamicum, the ortholog of cpsA1 is the only gene involved in this function, and its conditional knockdown leads to dramatic changes in the cell wall composition and morphology of the bacteria due to extensive shedding of cell wall material in the culture medium as a result of defective attachment of AG to PG. This work marks an important step in our understanding of the biogenesis of the unique cell envelope of mycobacteria and opens new opportunities for drug development.

Footnotes

  • ↵2 These authors are co-senior authors.

  • ↵* This work was supported by NIAID, National Institutes of Health, Grant AI119670 and the College of Veterinary Medicine and Biomedical Sciences Research Council (Colorado State University). The electron microscopy work at C-CINA (Biozentrum) was supported in part by the Swiss National Science Foundation (SystemsX.ch RTD CINA and NCCR TransCure). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

  • ↵Graphic This article contains supplemental Table S1 and Figs. S1–S3.

  • Received May 26, 2016.
  • Revision received July 12, 2016.
View this article with LENS
Table of Contents

This Article

  1. First Published on July 14, 2016 doi: 10.1074/jbc.M116.739227 The Journal of Biological Chemistry 291, 18867-18879.
  1. » Abstract(Free)
  2. Full Text
  3. PDF
  4. PDF including Supp Data
  5. Supplemental Data
  6. All Versions of this Article:
    1. M116.739227v1
    2. 291/36/18867 (most recent)

Article Usage Stats

  1. Article Usage Statistics

Submit your work to JBC.

You'll be in good company.