Analysis of the Neurotoxin Complex Genes in Clostridium botulinum A1-A4 and B1 Strains: BoNT/A3, BoNT/Ba4 and BoNT/B1 Clusters Are Located within Plasmids

被引:124
作者
Smith, Theresa J. [2 ]
Hill, Karen K. [1 ]
Foley, Brian T. [3 ]
Detter, John C. [1 ]
Munk, A. Christine [1 ]
Bruce, David C. [1 ]
Doggett, Norman A. [1 ]
Smith, Leonard A. [2 ]
Marks, James D. [4 ]
Xie, Gary [1 ]
Brettin, Thomas S. [1 ]
机构
[1] Los Alamos Natl Lab, Biosci Div, Los Alamos, NM 87545 USA
[2] USA, Med Inst Infect Dis, Integrated Toxicol Div, Ft Detrick, MD USA
[3] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM USA
[4] Univ Calif San Francisco, Dept Anesthesia & Pharmaceut Chem, San Francisco, CA 94143 USA
来源
PLOS ONE | 2007年 / 2卷 / 12期
关键词
D O I
10.1371/journal.pone.0001271
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background. Clostridium botulinum and related clostridial species express extremely potent neurotoxins known as botulinum neurotoxins (BoNTs) that cause long-lasting, potentially fatal intoxications in humans and other mammals. The amino acid variation within the BoNT is used to categorize the species into seven immunologically distinct BoNT serotypes (A-G) which are further divided into subtypes. The BoNTs are located within two generally conserved gene arrangements known as botulinum progenitor complexes which encode toxin-associated proteins involved in toxin stability and expression. Methodology/Principal Findings. Because serotype A and B strains are responsible for the vast majority of human botulism cases worldwide, the location, arrangement and sequences of genes from eight different toxin complexes representing four different BoNT/A subtypes (BoNT/A1-Ba4) and one BoNT/B1 strain were examined. The bivalent Ba4 strain contained both the BoNT/A4 and BoNT/bvB toxin clusters. The arrangements of the BoNT/A3 and BoNT/A4 subtypes differed from the BoNT/A1 strains and were similar to those of BoNT/A2. However, unlike the BoNT/A2 subtype, the toxin complex genes of BoNT/A3 and BoNT/A4 were found within large plasmids and not within the chromosome. In the Ba4 strain, both BoNT toxin clusters (A4 and bivalent B) were located within the same 270 kb plasmid, separated by 97 kb. Complete genomic sequencing of the BoNT/B1 strain also revealed that its toxin complex genes were located within a 149 kb plasmid and the BoNT/A3 complex is within a 267 kb plasmid. Conclusions/Significance. Despite their size differences and the BoNT genes they contain, the three plasmids containing these toxin cluster genes share significant sequence identity. The presence of partial insertion sequence ( IS) elements, evidence of recombination/gene duplication events, and the discovery of the BoNT/A3, BoNT/Ba4 and BoNT/B1 toxin complex genes within plasmids illustrate the different mechanisms by which these genes move among diverse genetic backgrounds of C. botulinum.
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