Genetic diversity within the botulinum neurotoxin-producing bacteria and their neurotoxins
Abstract
The recent availability of multiple Clostridium botulinum genomic sequences has initiated a new genomics era that strengthens our understanding of the bacterial species that produce botulinum neurotoxins (BoNTs). Analysis of the genomes has reinforced the historical Group I–VI designations and provided evidence that the bont genes can be located within the chromosome, phage or plasmids. The sequences provide the opportunity to examine closely the variation among the toxin genes, the composition and organization of the toxin complex, the regions flanking the toxin complex and the location of the toxin within different bacterial strains. These comparisons provide evidence of horizontal gene transfer and site-specific insertion and recombination events that have contributed to the variation observed among the neurotoxins. In this work, examples that have contributed to the variation observed in serotypes A-H strains are presented to illustrate the mechanisms that have contributed to their variation.
- Authors:
-
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- US Army Medical Research Inst. of Infectious Diseases (USAMRIID), Fort Detrick, MD (United States). Molecular and Translational Sciences Division
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE National Nuclear Security Administration (NNSA); National Institutes of Health (NIH)
- OSTI Identifier:
- 1457238
- Report Number(s):
- LA-UR-15-23061
Journal ID: ISSN 0041-0101
- Grant/Contract Number:
- AC52-06NA25396; U01 AI056493
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Toxicon
- Additional Journal Information:
- Journal Volume: 107; Journal Issue: PA; Journal ID: ISSN 0041-0101
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; genetic diversity; botulinum neurotoxin; Clostridium botulinum
Citation Formats
Hill, Karen Koons, Xie, Gary, Foley, Brian T., and Smith, Theresa J. Genetic diversity within the botulinum neurotoxin-producing bacteria and their neurotoxins. United States: N. p., 2015.
Web. doi:10.1016/j.toxicon.2015.09.011.
Hill, Karen Koons, Xie, Gary, Foley, Brian T., & Smith, Theresa J. Genetic diversity within the botulinum neurotoxin-producing bacteria and their neurotoxins. United States. https://doi.org/10.1016/j.toxicon.2015.09.011
Hill, Karen Koons, Xie, Gary, Foley, Brian T., and Smith, Theresa J. Fri .
"Genetic diversity within the botulinum neurotoxin-producing bacteria and their neurotoxins". United States. https://doi.org/10.1016/j.toxicon.2015.09.011. https://www.osti.gov/servlets/purl/1457238.
@article{osti_1457238,
title = {Genetic diversity within the botulinum neurotoxin-producing bacteria and their neurotoxins},
author = {Hill, Karen Koons and Xie, Gary and Foley, Brian T. and Smith, Theresa J.},
abstractNote = {The recent availability of multiple Clostridium botulinum genomic sequences has initiated a new genomics era that strengthens our understanding of the bacterial species that produce botulinum neurotoxins (BoNTs). Analysis of the genomes has reinforced the historical Group I–VI designations and provided evidence that the bont genes can be located within the chromosome, phage or plasmids. The sequences provide the opportunity to examine closely the variation among the toxin genes, the composition and organization of the toxin complex, the regions flanking the toxin complex and the location of the toxin within different bacterial strains. These comparisons provide evidence of horizontal gene transfer and site-specific insertion and recombination events that have contributed to the variation observed among the neurotoxins. In this work, examples that have contributed to the variation observed in serotypes A-H strains are presented to illustrate the mechanisms that have contributed to their variation.},
doi = {10.1016/j.toxicon.2015.09.011},
journal = {Toxicon},
number = PA,
volume = 107,
place = {United States},
year = {Fri Sep 11 00:00:00 EDT 2015},
month = {Fri Sep 11 00:00:00 EDT 2015}
}
Web of Science
Works referenced in this record:
Three Classes of Plasmid (47–63 kb) Carry the Type B Neurotoxin Gene Cluster of Group II Clostridium botulinum
journal, July 2014
- Carter, Andrew T.; Austin, John W.; Weedmark, Kelly A.
- Genome Biology and Evolution, Vol. 6, Issue 8
Complete Genome Sequence of the Proteolytic Clostridium botulinum Type A5 (B3′) Strain H04402 065
journal, May 2011
- Carter, Andrew T.; Pearson, Bruce M.; Crossman, Lisa C.
- Journal of Bacteriology, Vol. 193, Issue 9
The Type F6 Neurotoxin Gene Cluster Locus of Group II Clostridium botulinum Has Evolved by Successive Disruption of Two Different Ancestral Precursors
journal, May 2013
- Carter, Andrew T.; Stringer, Sandra C.; Webb, Martin D.
- Genome Biology and Evolution, Vol. 5, Issue 5
Quantitative Real-Time Reverse Transcription-PCR Analysis Reveals Stable and Prolonged Neurotoxin Cluster Gene Activity in a Clostridium botulinum Type E Strain at Refrigeration Temperature
journal, October 2008
- Chen, Ying; Korkeala, Hannu; Lindén, Jere
- Applied and Environmental Microbiology, Vol. 74, Issue 19
Regulation of toxin synthesis in Clostridium botulinum and Clostridium tetani
journal, December 2013
- Connan, Chloé; Denève, Cécile; Mazuet, Christelle
- Toxicon, Vol. 75
Arrangement of the Clostridium baratii F7 Toxin Gene Cluster with Identification of a σ Factor That Recognizes the Botulinum Toxin Gene Cluster Promoters
journal, May 2014
- Dover, Nir; Barash, Jason R.; Burke, Julianne N.
- PLoS ONE, Vol. 9, Issue 5
Clostridium botulinum Strain Af84 Contains Three Neurotoxin Gene Clusters: Bont/A2, bont/F4 and bont/F5
journal, April 2013
- Dover, Nir; Barash, Jason R.; Hill, Karen K.
- PLoS ONE, Vol. 8, Issue 4
Molecular Characterization of a Novel Botulinum Neurotoxin Type H Gene
journal, October 2013
- Dover, Nir; Barash, Jason R.; Hill, Karen K.
- The Journal of Infectious Diseases, Vol. 209, Issue 2
Organization and Phylogenetic Interrelationships of Genes Encoding Components of the Botulinum Toxin Complex in Proteolytic Clostridium botulinum Types A, B, and F: Evidence of Chimeric Sequences in the Gene Encoding the Nontoxic Nonhemagglutinin Component
journal, October 1996
- East, A. K.; Bhandari, M.; Stacey, J. M.
- International Journal of Systematic Bacteriology, Vol. 46, Issue 4
Evidence that Plasmid-Borne Botulinum Neurotoxin Type B Genes Are Widespread among Clostridium botulinum Serotype B Strains
journal, March 2009
- Franciosa, Giovanna; Maugliani, Antonella; Scalfaro, Concetta
- PLoS ONE, Vol. 4, Issue 3
Draft Genome Sequence of Bivalent Clostridium botulinum Strain IBCA10-7060, Encoding Botulinum Neurotoxin B and a New FA Mosaic Type
journal, November 2014
- Gonzalez-Escalona, N.; Thirunavukkarasu, N.; Singh, A.
- Genome Announcements, Vol. 2, Issue 6
Organization of the botulinum neurotoxin C1 gene and its associated non-toxic protein genes in Clostridium botulinum C468
journal, November 1994
- Hauser, Daniel; Eklund, Mel W.; Boquet, Patrice
- Molecular and General Genetics MGG, Vol. 243, Issue 6
Genetic Diversity among Botulinum Neurotoxin-Producing Clostridial Strains
journal, November 2006
- Hill, K. K.; Smith, T. J.; Helma, C. H.
- Journal of Bacteriology, Vol. 189, Issue 3
Recombination and insertion events involving the botulinum neurotoxin complex genes in Clostridium botulinum types A, B, E and F and Clostridium butyricumtype E strains
journal, October 2009
- Hill, Karen K.; Xie, Gary; Foley, Brian T.
- BMC Biology, Vol. 7, Issue 1
Functional Characterization of Botulinum Neurotoxin Serotype H as a Hybrid of Known Serotypes F and A (BoNT F/A)
journal, March 2015
- Kalb, Suzanne R.; Baudys, Jakub; Raphael, Brian H.
- Analytical Chemistry, Vol. 87, Issue 7
Isolation and Functional Characterization of the Novel Clostridium botulinum Neurotoxin A8 Subtype
journal, February 2015
- Kull, Skadi; Schulz, K. Melanie; Strotmeier, Jasmin Weisemann née
- PLOS ONE, Vol. 10, Issue 2
Analysis of a unique Clostridium botulinum strain from the Southern hemisphere producing a novel type E botulinum neurotoxin subtype
journal, January 2012
- Raphael, Brian H.; Lautenschlager, Matthew; Kalb, Suzanne R.
- BMC Microbiology, Vol. 12, Issue 1
The genome sequence of Clostridium botulinum type C neurotoxin-converting phage and the molecular mechanisms of unstable lysogeny
journal, November 2005
- Sakaguchi, Y.; Hayashi, T.; Kurokawa, K.
- Proceedings of the National Academy of Sciences, Vol. 102, Issue 48
Genomic sequences of six botulinum neurotoxin-producing strains representing three clostridial species illustrate the mobility and diversity of botulinum neurotoxin genes
journal, March 2015
- Smith, Theresa J.; Hill, Karen K.; Xie, Gary
- Infection, Genetics and Evolution, Vol. 30
Molecular Characterization of Clostridium botulinum Isolates from Foodborne Outbreaks in Thailand, 2010
journal, January 2014
- Wangroongsarb, Piyada; Kohda, Tomoko; Jittaprasartsin, Chutima
- PLoS ONE, Vol. 9, Issue 1
Protection with recombinant Clostridium botulinum C1 and D binding domain subunit (Hc) vaccines against C and D neurotoxins
journal, May 2007
- Webb, Robert P.; Smith, Theresa J.; Wright, Patrick M.
- Vaccine, Vol. 25, Issue 21
Two Novel Toxin Variants Revealed by Whole-Genome Sequencing of 175 Clostridium botulinum Type E Strains
journal, August 2014
- Weedmark, K. A.; Lambert, D. L.; Mabon, P.
- Applied and Environmental Microbiology, Vol. 80, Issue 20
Plasmid-Borne Type E Neurotoxin Gene Clusters in Clostridium botulinum Strains
journal, April 2013
- Zhang, Zhen; Hintsa, Hannamari; Chen, Ying
- Applied and Environmental Microbiology, Vol. 79, Issue 12
Works referencing / citing this record:
A Rapid, Sensitive, and Portable Biosensor Assay for the Detection of Botulinum Neurotoxin Serotype A in Complex Food Matrices
journal, November 2018
- Tam, Christina; Flannery, Andrew; Cheng, Luisa
- Toxins, Vol. 10, Issue 11
Engineered botulinum neurotoxin B with improved efficacy for targeting human receptors
journal, July 2017
- Tao, Liang; Peng, Lisheng; Berntsson, Ronnie P. -A.
- Nature Communications, Vol. 8, Issue 1
PCR-based molecular diagnosis of botulism (types C and D) outbreaks in aquatic birds
journal, October 2018
- Chellapandi, Paulchamy; Prisilla, Arockiasamy
- Annals of Microbiology, Vol. 68, Issue 12
Identification of a novel botulinum neurotoxin gene cluster in Enterococcus
journal, January 2018
- Brunt, Jason; Carter, Andrew T.; Stringer, Sandra C.
- FEBS Letters, Vol. 592, Issue 3
Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin DC
journal, November 2017
- Zhang, Sicai; Berntsson, Ronnie P. -A.; Tepp, William H.
- Nature Communications, Vol. 8, Issue 1
Critical Analysis of Neuronal Cell and the Mouse Bioassay for Detection of Botulinum Neurotoxins
journal, December 2019
- Pellett, Sabine; Tepp, William H.; Johnson, Eric A.
- Toxins, Vol. 11, Issue 12
Engineering of Botulinum Neurotoxins for Biomedical Applications
journal, June 2018
- Webb, Robert
- Toxins, Vol. 10, Issue 6
The Light Chain Defines the Duration of Action of Botulinum Toxin Serotype A Subtypes
journal, March 2018
- Pellett, Sabine; Bradshaw, Marite; Tepp, William H.
- mBio, Vol. 9, Issue 2
Why Are Botulinum Neurotoxin-Producing Bacteria So Diverse and Botulinum Neurotoxins So Toxic?
journal, January 2019
- Poulain, Bernard; Popoff, Michel
- Toxins, Vol. 11, Issue 1
The Novel Clostridial Neurotoxin Produced by Strain IBCA10-7060 Is Immunologically Equivalent to BoNT/HA
journal, December 2019
- Fan, Yongfeng; Barash, Jason R.; Conrad, Fraser
- Toxins, Vol. 12, Issue 1
Identification and characterization of a novel botulinum neurotoxin
journal, August 2017
- Zhang, Sicai; Masuyer, Geoffrey; Zhang, Jie
- Nature Communications, Vol. 8, Issue 1
Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature
journal, January 2017
- Peck, Michael; Smith, Theresa; Anniballi, Fabrizio
- Toxins, Vol. 9, Issue 1
Microbiota Signaling Pathways that Influence Neurologic Disease
journal, January 2018
- Cox, Laura M.; Weiner, Howard L.
- Neurotherapeutics, Vol. 15, Issue 1
The orphan germinant receptor protein GerXAO (but not GerX3b) is essential for L-alanine induced germination in Clostridium botulinum Group II
journal, May 2018
- Brunt, Jason; Carter, Andrew T.; Pye, Hannah V.
- Scientific Reports, Vol. 8, Issue 1
In silico mutagenesis: decreasing the immunogenicity of botulinum toxin type A
journal, January 2019
- Evander Emeltan Tjoa, Stanley; Maria Vianney, Yoanes; Emantoko Dwi Putra, Sulistyo
- Journal of Biomolecular Structure and Dynamics, Vol. 37, Issue 18
Diversity of Group I and II Clostridium botulinum Strains from France Including Recently Identified Subtypes
journal, April 2016
- Mazuet, Christelle; Legeay, Christine; Sautereau, Jean
- Genome Biology and Evolution, Vol. 8, Issue 6
In silico mutagenesis: decreasing the immunogenicity of botulinum toxin type A
text, January 2019
- Tjoa, Stanley Evander Emeltan; Vianney, Yoanes Maria; Putra, Sulistyo Emantoko Dwi
- Taylor & Francis
A Rapid, Sensitive, and Portable Biosensor Assay for the Detection of Botulinum Neurotoxin Serotype A in Complex Food Matrices
posted_content, August 2018
- Tam, Christina C.; Flannery, Andrew R.; Cheng, Luisa W.
- Preprints.org
In silico mutagenesis: decreasing the immunogenicity of botulinum toxin type A
text, January 2019
- Tjoa, Stanley Evander Emeltan; Vianney, Yoanes Maria; Putra, Sulistyo Emantoko Dwi
- Taylor & Francis
Identification of a novel botulinum neurotoxin gene cluster in Enterococcus
journal, January 2018
- Brunt, Jason; Carter, Andrew T.; Stringer, Sandra C.
- FEBS Letters, Vol. 592, Issue 3
Engineered botulinum neurotoxin B with improved efficacy for targeting human receptors
journal, July 2017
- Tao, Liang; Peng, Lisheng; Berntsson, Ronnie P. -A.
- Nature Communications, Vol. 8, Issue 1
The orphan germinant receptor protein GerXAO (but not GerX3b) is essential for L-alanine induced germination in Clostridium botulinum Group II
journal, May 2018
- Brunt, Jason; Carter, Andrew T.; Pye, Hannah V.
- Scientific Reports, Vol. 8, Issue 1
The pattern of growth observed forClostridium botulinumtype A1 strain ATCC 19397 is influenced by nutritional status and quorum sensing: a modelling perspective
journal, October 2015
- Ihekwaba, Adaoha E. C.; Mura, Ivan; Peck, Michael W.
- Pathogens and Disease, Vol. 73, Issue 9
Diversity of Group I and II Clostridium botulinum Strains from France Including Recently Identified Subtypes
journal, April 2016
- Mazuet, Christelle; Legeay, Christine; Sautereau, Jean
- Genome Biology and Evolution, Vol. 8, Issue 6
Characterization of a membrane binding loop leads to engineering botulinum neurotoxin B with improved therapeutic efficacy
journal, March 2020
- Yin, Linxiang; Masuyer, Geoffrey; Zhang, Sicai
- PLOS Biology, Vol. 18, Issue 3
A Rapid, Sensitive, and Portable Biosensor Assay for the Detection of Botulinum Neurotoxin Serotype A in Complex Food Matrices
posted_content, August 2018
- Tam, Christina C.; Flannery, Andrew R.; Cheng, Luisa W.
- Preprints.org
Diversity of the Germination Apparatus in Clostridium botulinum Groups I, II, III, and IV
journal, October 2016
- Brunt, Jason; van Vliet, Arnoud H. M.; van den Bos, Fédor
- Frontiers in Microbiology, Vol. 7
Engineering of Botulinum Neurotoxins for Biomedical Applications
journal, June 2018
- Webb, Robert
- Toxins, Vol. 10, Issue 6
Why Are Botulinum Neurotoxin-Producing Bacteria So Diverse and Botulinum Neurotoxins So Toxic?
journal, January 2019
- Poulain, Bernard; Popoff, Michel
- Toxins, Vol. 11, Issue 1
Critical Analysis of Neuronal Cell and the Mouse Bioassay for Detection of Botulinum Neurotoxins
journal, December 2019
- Pellett, Sabine; Tepp, William H.; Johnson, Eric A.
- Toxins, Vol. 11, Issue 12
The Novel Clostridial Neurotoxin Produced by Strain IBCA10-7060 Is Immunologically Equivalent to BoNT/HA
journal, December 2019
- Fan, Yongfeng; Barash, Jason R.; Conrad, Fraser
- Toxins, Vol. 12, Issue 1
Probiotic Microorganisms Inhibit Epithelial Cell Internalization of Botulinum Neurotoxin Serotype A
journal, December 2016
- Lam, Tina; Tam, Christina; Stanker, Larry
- Toxins, Vol. 8, Issue 12
Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature
journal, January 2017
- Peck, Michael; Smith, Theresa; Anniballi, Fabrizio
- Toxins, Vol. 9, Issue 1
Vaccines against Botulism
journal, September 2017
- Sundeen, Grace; Barbieri, Joseph
- Toxins, Vol. 9, Issue 9