Interference of Mycobacterium tuberculosis cell division by Rv2719c, a cell wall hydrolase

Mol Microbiol. 2006 Oct;62(1):132-47. doi: 10.1111/j.1365-2958.2006.05333.x. Epub 2006 Aug 30.


The genetic factors responsible for the regulation of cell division in Mycobacterium tuberculosis are largely unknown. We showed that exposure of M. tuberculosis to DNA damaging agents, or to cephalexin, or growth of M. tuberculosis in macrophages increased cell length and sharply elevated the expression of Rv2719c, a LexA-controlled gene. Overexpression of Rv2719c in the absence of DNA damage or of antibiotic treatment also led to filamentation and reduction in viability both in broth and in macrophages indicating a correlation between Rv2719c levels and cell division. Overproduction of Rv2719c compromised midcell localization of FtsZ rings, but had no effect on the intracellular levels of FtsZ. In vitro, the Rv2719c protein did not interfere with the GTP-dependent polymerization activity of FtsZ indicating that the effects of Rv2719c on Z-ring assembly are indirect. Rv2719c protein exhibited mycobacterial murein hydrolase activity that was localized to the N-terminal 110 amino acids. Visualization of nascent peptidoglycan (PG) synthesis zones by probing with fluoresceinated vancomycin (Van-FL) and localization of green fluorescent protein-Rv2719c fusion suggested that the Rv2719c activity is targeted to potential PG synthesis zones. We propose that Rv2719c is a potential regulator of M. tuberculosis cell division and that its levels, and possibly activities, are modulated under a variety of growth conditions including growth in vivo and during DNA damage, so that the assembly of FtsZ-rings, and therefore the cell division, can proceed in a regulated manner.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Division / drug effects
  • Cell Division / genetics
  • Cell Division / physiology
  • Cell Line
  • Cell Survival
  • Cell Wall / metabolism*
  • Cells, Cultured
  • Cephalexin / pharmacology
  • Cloning, Molecular
  • Gene Expression Regulation, Bacterial / drug effects
  • Gene Expression Regulation, Bacterial / genetics
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / genetics
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Hydrolases / genetics
  • Hydrolases / metabolism*
  • Hydrolysis / drug effects
  • Immunoblotting
  • Macrophages / cytology
  • Macrophages / microbiology
  • Microscopy, Fluorescence
  • Mutation / genetics
  • Mycobacterium tuberculosis / enzymology*
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / growth & development
  • N-Acetylmuramoyl-L-alanine Amidase / genetics
  • N-Acetylmuramoyl-L-alanine Amidase / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Hydrolases
  • N-Acetylmuramoyl-L-alanine Amidase
  • Cephalexin