Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA.
J Biol Chem. 2010 Sep 3;285(36):28220-8. doi: 10.1074/jbc.M110.118554. Epub 2010 Jun 25.
Through elaboration of its botulinum toxins, Clostridium botulinum produces clinical syndromes of infant botulism, wound botulism, and other invasive infections. Using comparative genomic analysis, an orphan nine-gene cluster was identified in C. botulinum and the related foodborne pathogen Clostridium sporogenes that resembled the biosynthetic machinery for streptolysin S, a key virulence factor from group A Streptococcus responsible for its hallmark beta-hemolytic phenotype. Genetic complementation, in vitro reconstitution, mass spectral analysis, and plasmid intergrational mutagenesis demonstrate that the streptolysin S-like gene cluster from Clostridium sp. is responsible for the biogenesis of a novel post-translationally modified hemolytic toxin, clostridiolysin S.
通过对其肉毒梭菌毒素的阐述，肉毒梭菌产生了婴儿肉毒中毒、创伤肉毒中毒和其他侵袭性感染的临床综合征。利用比较基因组分析，在肉毒梭菌和相关的食源性病原体生孢梭菌中鉴定出一个孤儿九基因簇，该簇类似于链球菌溶血素 S 的生物合成机制，链球菌溶血素 S 是 A 组链球菌的关键毒力因子，负责其标志性的β-溶血表型。遗传互补、体外重建、质谱分析和质粒整合诱变证明，来自梭菌的链球菌溶血素 S 样基因簇负责一种新型翻译后修饰的溶血毒素——梭菌溶血素 S 的生物发生。
