Clostridiolysin S, a Post-translationally Modified Biotoxin from Clostridium botulinum

被引:53
作者
Gonzalez, David J. [2 ]
Lee, Shaun W. [9 ]
Hensler, Mary E. [6 ]
Markley, Andrew L. [2 ]
Dahesh, Samira [6 ]
Mitchell, Douglas A. [10 ,11 ,12 ]
Bandeira, Nuno [7 ]
Nizet, Victor [1 ,6 ]
Dixon, Jack E. [2 ,4 ,5 ,8 ]
Dorrestein, Pieter C. [1 ,2 ,3 ,4 ]
机构
[1] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Ctr Marine Biotechnol & Biomed, La Jolla, CA 92093 USA
[4] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
[5] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
[6] Univ Calif San Diego, Div Pharmacol & Drug Discovery, Dept Pediat, La Jolla, CA 92093 USA
[7] Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USA
[8] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA
[9] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA
[10] Univ Illinois, Dept Chem, Urbana, IL 61801 USA
[11] Univ Illinois, Dept Microbiol, Urbana, IL 61801 USA
[12] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA
基金
美国国家卫生研究院;
关键词
STREPTOLYSIN-S; MASS-SPECTROMETRY; MICROCIN C7; BIOSYNTHESIS; PEPTIDE; STREPTOCOCCUS; IDENTIFICATION; SPOROGENES; COMPONENT; PATHWAY;
D O I
10.1074/jbc.M110.118554
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:28220 / 28228
页数:9
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