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Genetic Diversity Within Clostridium botulinum Serotypes, Botulinum Neurotoxin Gene Clusters and Toxin Subtypes

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Botulinum Neurotoxins

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 364))

Abstract

Clostridium botulinum is a species of spore-forming anaerobic bacteria defined by the expression of any one or two of seven serologically distinct botulinum neurotoxins (BoNTs) designated BoNT/A-G. This Gram-positive bacterium was first identified in 1897 and since then the paralyzing and lethal effects of its toxin have resulted in the recognition of different forms of the intoxication known as food-borne, infant, or wound botulism. Early microbiological and biochemical characterization of C. botulinum isolates revealed that the bacteria within the species had different characteristics and expressed different toxin types. To organize the variable bacterial traits within the species, Group I–IV designations were created. Interestingly, it was observed that isolates within different Groups could express the same toxin type and conversely a single Group could express different toxin types. This discordant phylogeny between the toxin and the host bacteria indicated that horizontal gene transfer of the toxin was responsible for the variation observed within the species. The recent availability of multiple C. botulinum genomic sequences has offered the ability to bioinformatically analyze the locations of the bont genes, the composition of their toxin gene clusters, and the genes flanking these regions to understand their variation. Comparison of the genomic sequences representing multiple serotypes indicates that the bont genes are not in random locations. Instead the analyses revealed specific regions where the toxin genes occur within the genomes representing serotype A, B, C, E, and F C. botulinum strains and C. butyricum type E strains. The genomic analyses have provided evidence of horizontal gene transfer, site-specific insertion, and recombination events. These events have contributed to the variation observed among the neurotoxins, the toxin gene clusters and the bacteria that contain them, and has supported the historical microbiological, and biochemical characterization of the Group classification within the species.

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Abbreviations

BoNT:

Botulinum neurotoxin

HA:

Hemagglutinin

NTNHA:

Non-toxic nonhemagglutinin

orf:

Open reading frame

bp:

Base pair

kb:

Kilobase

Mb:

Megabase

IS elements:

Insertion sequence elements

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Acknowledgments

Funding for this research was provided by the Department of Homeland Security Science and Technology Directorate contract HSHQDC-10-C-00139 and NIAID IAA 120.B18. Los Alamos National Laboratory strongly supports academic freedom and a researcher’s right to publish; however the Laboratory as an institution does not necessarily endorse the viewpoint of a publication or guarantee its technical correctness. Opinions, interpretations, conclusions and recommendations are those of the authors and not necessarily endorsed by the U.S. Army, the National Institute of Allergy and Infectious Diseases, or the National Institutes of Health.

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Authors and Affiliations

  1. Los Alamos National Laboratory, Mail Stop: M 888, Los Alamos, NM, 87545, USA

    Karen K. Hill

  2. United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD, USA

    Theresa J. Smith

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  1. Karen K. Hill
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Correspondence to Karen K. Hill .

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Editors and Affiliations

  1. , Institut für Toxikologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, Hannover, 30625, Germany

    Andreas Rummel

  2. , Institut für Physiologische Chemie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, Hannover, 30625, Germany

    Thomas Binz

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Hill, K.K., Smith, T.J. (2012). Genetic Diversity Within Clostridium botulinum Serotypes, Botulinum Neurotoxin Gene Clusters and Toxin Subtypes. In: Rummel, A., Binz, T. (eds) Botulinum Neurotoxins. Current Topics in Microbiology and Immunology, vol 364. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-33570-9_1

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