Capsule anchoring in Bacillus anthracis occurs by a transpeptidation reaction that is inhibited by capsidin

Mol Microbiol. 2009 Jan;71(2):404-20. doi: 10.1111/j.1365-2958.2008.06533.x. Epub 2008 Nov 11.


Bacillus anthracis, the causative agent of anthrax, is a dangerous biological weapon, as spores derived from drug-resistant strains cause infections for which antibiotic therapy is no longer effective. We sought to develop an anti-infective therapy for anthrax and targeted CapD, an enzyme that cleaves poly-gamma-D-glutamate capsule and generates amide bonds with peptidoglycan cross-bridges to deposit capsular material into the envelope of B. anthracis. In agreement with the model that capsule confers protection from phagocytic clearance, B. anthracis capD variants failed to deposit capsule into the envelope and displayed defects in anthrax pathogenesis. By screening chemical libraries, we identified the CapD inhibitor capsidin, 4-[(4-bromophenyl)thio]-3-(diacetylamino)benzoic acid), which covalently modifies the active-site threonine of the transpeptidase. Capsidin treatment blocked capsular assembly by B. anthracis and enabled phagocytic killing of non-encapsulated vegetative forms.

Publication types

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

MeSH terms

  • Aminobenzoates / pharmacology*
  • Animals
  • Anthrax / microbiology*
  • Anti-Bacterial Agents / pharmacology
  • Bacillus anthracis / drug effects
  • Bacillus anthracis / enzymology*
  • Bacillus anthracis / genetics
  • Bacillus anthracis / pathogenicity
  • Bacterial Capsules / drug effects
  • Bacterial Capsules / metabolism*
  • Female
  • Guinea Pigs
  • Peptidoglycan / metabolism*
  • Peptidyl Transferases / genetics
  • Peptidyl Transferases / metabolism*
  • Polyglutamic Acid / analogs & derivatives
  • Polyglutamic Acid / metabolism
  • Sulfides / pharmacology*
  • Virulence


  • 4-((4-bromophenyl)thio)-3-(diacetylamino)benzoic acid
  • Aminobenzoates
  • Anti-Bacterial Agents
  • Peptidoglycan
  • Sulfides
  • poly(gamma-glutamic acid)
  • Polyglutamic Acid
  • Peptidyl Transferases