CSDB: Search results

Taxonomic group: bacteria / Firmicutes (Phylum: Firmicutes)
Associated disease: anthrax [ICD11: 1B97

, ICD11: XN94F

]; infection due to Bacillus anthracis [ICD11: XN94F

]

NCBI PubMed ID: 29229702
Publication DOI: 10.1128/JB.00562-17
Journal NLM ID: 2985120R
Publisher: American Society for Microbiology
Correspondence: oschnee

bsd.uchicago.edu
Institutions: Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Lemont, Illinois, USA, Department of Microbiology, University of Chicago, Chicago, Illinois, USA, Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA, Headquarters, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Bacillus anthracis, the causative agent of anthrax disease, elaborates a secondary cell wall polysaccharide (SCWP) that is essential for bacterial growth and cell division. B. anthracis SCWP is comprised of trisaccharide repeats with the structure, [→4)-β-ManNAc-(1→4)-β-GlcNAc(O3-α-Gal)-(1→6)-α-GlcNAc(O3-α-Gal, O4-β-Gal)-(1→]6-12 The genes whose products promote the galactosylation of B. anthracis SCWP are not yet known. We show here that the expression of galE1, encoding a UDP-glucose 4-epimerase necessary for the synthesis of UDP-galactose, is required for B. anthracis SCWP galactosylation. The galE1 mutant assembles surface (S) layer and S layer-associated proteins that associate with ketal-pyruvylated SCWP via their S layer homology domains similarly to wild-type B. anthracis, but the mutant displays a defect in γ-phage murein hydrolase binding to SCWP. Furthermore, deletion of galE1 diminishes the capsulation of B. anthracis with poly-d-γ-glutamic acid (PDGA) and causes a reduction in bacterial virulence. These data suggest that SCWP galactosylation is required for the physiologic assembly of the B. anthracis cell wall envelope and for the pathogenesis of anthrax disease. IMPORTANCE Unlike virulent Bacillus anthracis isolates, B. anthracis strain CDC684 synthesizes secondary cell wall polysaccharide (SCWP) trisaccharide repeats without galactosyl modification, exhibits diminished growth in vitro in broth cultures, and is severely attenuated in an animal model of anthrax. To examine whether SCWP galactosylation is a requirement for anthrax disease, we generated variants of B. anthracis strains Sterne 34F2 and Ames lacking UDP-glucose 4-epimerase by mutating the genes galE1 and galE2 We identified galE1 as necessary for SCWP galactosylation. Deletion of galE1 decreased the poly-d-γ-glutamic acid (PDGA) capsulation of the vegetative form of B. anthracis and increased the bacterial inoculum required to produce lethal disease in mice, indicating that SCWP galactosylation is indeed a determinant of anthrax disease.

cell wall, capsule, S layer, Bacillus anthracis, GalE1, poly-d-γ-glutamic acid, secondary cell wall polysaccharide, UDP-glucose 4-epimerase

Structure type: polymer chemical repeating unit ; n=6-12
Location inside paper: abstract
Contained glycoepitopes: IEDB_135813,IEDB_136044,IEDB_136906,IEDB_137340,IEDB_137472,IEDB_140108,IEDB_141794,IEDB_141807,IEDB_151528,IEDB_151531,IEDB_190606,IEDB_885813,SB_165,SB_166,SB_187,SB_195,SB_30,SB_7,SB_88

Methods: PCR, MALDI-TOF MS, genetic methods, RP-HPLC, immunofluorescence labeling
Comments, role: published polymerization frame was shifted for conformity with other records

Related record ID(s): 12884, 13113
NCBI Taxonomy refs (TaxIDs): 1392
Reference(s) to other database(s): GTC:G33812YG
Show glycosyltransferases

There is only one chemically distinct structure:

*OC[C@H]1O[C@H](O[C@@H]2[C@@H](CO)O[C@@H](O[C@@H]3[C@@H](CO)O[C@@H](*)[C@H](NC(C)=O)[C@H]3O[C@H]3O[C@H](CO)[C@H](O)[C@H](O)[C@H]3O)[C@@H](NC(C)=O)[C@H]2O)[C@H](NC(C)=O)[C@@H](O[C@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@@H]1O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O

SVG MW SMILES 3D mol Ionize