Taxonomic group: bacteria / Firmicutes (Phylum: Firmicutes)
Associated disease: infection due to Clostridium perfringens [ICD11: XN7J5 ]
 
NCBI PubMed ID: 32424044
Publication DOI: 10.1074/jbc.RA119.009978
Journal NLM ID: 2985121R
Publisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Correspondence: Christine M. Szymanski <cszymansuga.edu>
Institutions: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada, Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada, VaxAlta Inc., Edmonton, AB, Canada, Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada, Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia, USA, Department of Molecular Microbiology, Washington University of Medicine, St. Louis, Missouri, USA

Clostridium perfringens is a leading cause of food-poisoning and causes avian necrotic enteritis, posing a significant problem to both the poultry industry and human health. No effective vaccine against C. perfringens is currently available. Using an antiserum screen of mutants generated from a C. perfringens transposon-mutant library, here we identified an immunoreactive antigen that was lost in a putative glycosyltransferase mutant, suggesting that this antigen is likely a glycoconjugate. Following injection of formalin-fixed whole cells of C. perfringens HN13 (a laboratory strain) and JGS4143 (chicken isolate) intramuscularly into chickens, the HN13-derived antiserum was cross-reactive in immunoblots with all tested 32 field isolates, whereas only 5 of 32 isolates were recognized by JGS4143-derived antiserum. The immunoreactive antigens from both HN13 and JGS4143 were isolated, and structural analysis by MALDI-TOF-MS, GC-MS, and 2D NMR revealed that both were atypical lipoteichoic acids (LTAs) with poly-(β1→4)-ManNAc backbones substituted with phosphoethanolamine. However, although the ManNAc residues in JGS4143 LTA were phosphoethanolamine-modified, a few of these residues were instead modified with phosphoglycerol in the HN13 LTA. The JGS4143 LTA also had a terminal ribose and ManNAc instead of ManN in the core region, suggesting that these differences may contribute to the broadly cross-reactive response elicited by HN13. In a passive-protection chicken experiment, oral challenge with C. perfringens JGS4143 lead to 22% survival, whereas co-gavage with JGS4143 and α-HN13 antiserum resulted in 89% survival. This serum also induced bacterial killing in opsonophagocytosis assays, suggesting that HN13 LTA is an attractive target for future vaccine-development studies.

glycoconjugate vaccines, NMR spectroscopy, gram-positive bacteria, Clostridium perfringens, cell surface, lipoteichoic acid (LTA), food safety, one health, necrotic enteritis, foodborne illness

Structure type: structural motif or average structure
Location inside paper: p.9514
Trivial name: lipoteichoic acid
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_120354,IEDB_123890,IEDB_142488,IEDB_146664,IEDB_149136,IEDB_885813,IEDB_983931,SB_192
 
Methods: 13C NMR, 1H NMR, NMR-2D, GC-MS, SDS-PAGE, 31P NMR, deacylation, Western blotting, MALDI-TOF MS, composition analysis, serological methods, HF treatment, SEC, fluorescence microscopy, opsonophagocytosis assay
 
Related record ID(s): 7644, 7645, 7646, 32231
NCBI Taxonomy refs (TaxIDs): 195103
Reference(s) to other database(s): GTC:G30166OQ
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