N -Acetylglucosamine Deacetylases Modulate the Anchoring of the Gamma-Glutamyl Capsule to the Cell Wall of Bacillus anthracis
Year: 2014
Type: article
Abstract: Bacillus anthracis has a complex cell wall structure composed of a peptidoglycan (PG) layer to which major structures are anchored such as a neutral polysaccharide, an S-layer, and a poly-γ-D-glutamate (PDGA) capsule. Many of these structures have central roles in the biology of B. anthracis, particularly, in virulence. However, little attention has been devoted to structurally study the PG and how it is modified in the presence of these secondary cell wall components. We present here the fine structure of the PG of the encapsulated RPG1 strain harboring both pXO1 and pXO2 virulence plasmids. We show that B. anthracis has a high degree of cross-linking and its GlcNAc residues are highly modified by N-deacetylation. The PG composition is not dependent on the presence of either LPXTG proteins or the capsule. Using NMR analysis of the PG-PDGA complex, we provide evidence for the anchoring of the PDGA to the glucosamine residues. We show that anchoring of the PDGA capsule is impaired in two PG N-deacetylase mutants, Ba1961 and Ba3679. Thus, these multiple N-deactylase activities would constitute excellent drug targets in B. anthracis by simultaneously affecting its resistance to lysozyme and to phagocytosis impairing B. anthracis survival in the host.
Source: Microbial Drug Resistance
Institutions: Centre National de la Recherche Scientifique, Institut Pasteur, University of Crete, Inserm, FORTH Institute of Molecular Biology and Biotechnology, Université Joseph Fourier, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, CEA Grenoble, Institut de Biologie Structurale
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W2093666047