Premium
Capsule anchoring in Bacillus anthracis occurs by a transpeptidation reaction that is inhibited by capsidin
Author(s) -
Richter Stefan,
Anderson Valerie J.,
Garufi Gabriella,
Lu Lianghua,
Budzik Jonathan M.,
Joachimiak Andrzej,
He Chuan,
Schneewind Olaf,
Missiakas Dominique
Publication year - 2009
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2008.06533.x
Subject(s) - bacillus anthracis , microbiology and biotechnology , biology , peptidoglycan , capsule , antibiotics , enzyme , biochemistry , bacteria , genetics , botany
Summary 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‐γ‐ 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.