期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 295, 期 28, 页码 9513-9530出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA119.009978
关键词
Clostridium perfringens; lipoteichoic acid (LTA); food safety; one health; NMR spectroscopy; cell surface; Gram-positive bacteria; necrotic enteritis; glycoconjugate vaccines; foodborne illness; glycoconjugate; glycobiology; glycolipid structure; cell wall; carbohydrate biosynthesis; carbohydrate structure; microbiology; microbial pathogenesis
资金
- Alberta Livestock and Meat Agency
- Industrial Research Assistance Program
- Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, U.S. Department of Energy [DE-SC0015662]
Clostridium perfringensis 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 againstC. perfringensis currently available. Using an antiserum screen of mutants generated from aC. perfringenstransposon-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 ofC. perfringensHN13 (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-(?1?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 withC. perfringensJGS4143 lead to 22% survival, whereas co-gavage with JGS4143 and ?-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.
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