N-acetylglucosamine deacetylases modulate the anchoring of the gamma-glutamyl capsule to the cell wall of Bacillus anthracis.
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.
1 Institut Pasteur , Unité Toxines et Pathogénie Bactérienne, Paris, France .
Thomas
T
Candela
Stavroula
S
Balomenou
Willy
W
Aucher
Vassilis
V
Bouriotis
Jean-Pierre
JP
Simore
Agnes
A
Fouet
Ivo G
IG
Boneca
D000117:Acetylglucosamine / Q000737:chemistry / Q000378:metabolism*; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001408:Bacillus anthracis / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D015870:Gene Expression; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009113:Muramidase / Q000494:pharmacology; D009154:Mutation; D010457:Peptidoglycan / Q000378:metabolism; D010957:Plasmids; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D007527:Isoenzymes; D010457:Peptidoglycan; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D009113:Muramidase; D000581:Amidohydrolases; C023079:N-acetylglucosamine deacetylase; D000117:Acetylglucosamine