Botulinum Neurotoxin (BoNT) Resource Guide

BoNT References

PubMed Queries by Topic

To view the latest publications related to Clostridium botulinum, follow the provided pre-computed PubMed queries for Clostridium botulinum neurotoxins, toxin genes and strains, antibodies, inhibitors, and protocols. Additionally, selected references are found on this page under each subject heading. BoNT references listed here can be downloaded in PDF format by clicking:

• PubMed search: Clostridium botulinum
• PubMed search: Clostridium botulinum antibodies
• PubMed search: Clostridium botulinum genes
• PubMed search: Clostridium botulinum inhibitors
• PubMed search: Clostridium botulinum neurotoxin
• PubMed search: Clostridium botulinum protocols
• PubMed search: Clostridium botulinum strains

Selected Clostridium botulinum References

• Arnon SS et al. 2001: Botulinum toxin as a biological weapon: medical and public health management   
• Brin MF 1997: Botulinum Toxin: Chemistry, Pharmacology, Toxicity, and Immunology: Spasticity, Etiology, Evaluation, Management, and the Role of Botulinum Toxin Type A (Chapter 9)   
• Caya JG et al. 2004: Clostridium botulinum and the clinical laboratorian: a detailed review of botulism, including biological warfare ramifications of botulinum toxin  
• CDC: Botulism in the United States, 1899-1996  
• Keller JE 2006: Recovery from botulinum neurotoxin poisoning in vivo
• Keller JE et al. 2004: Uptake of botulinum neurotoxin into cultured neurons
• Montecucco C and Molgo J 2005: Botulinal neurotoxins: revival of an old killer
• Simpson LL 2004: Identification of the major steps in botulinum toxin action
• Ting PT and Frieman A 2004: The story of Clostridium botulinum: from food poisoning to Botox

Antibody References

• Almquist KC et al. 2006: Expression of an anti-botulinum toxin A neutralizing single-chain Fv recombinant antibody in transgenic tobacco
• Doellgast GJ et al. 1997: Sensitive assay for measurement of antibodies to Clostridium botulinum neurotoxins A, B, and E: use of hapten-labeled-antibody elution to isolate specific complexes  
• Keller JE et al. 1999: Rapid microplate assay for monitoring botulinum neurotoxin B catalytic activity
• Noah CW et al. 1995: Production of monoclonal antibodies specific to Clostridium botulinum type B neurotoxin
• Razai A et al. 2005: Molecular evolution of antibody affinity for sensitive detection of botulinum neurotoxin type A
• Smith TJ et al. 2005: Sequence variation within botulinum neurotoxin serotypes impacts antibody binding and neutralization  
• Summary of the NIAID expert panel on Botulinum neurotoxins therapeutics  
• Wu HC et al. 2001: Characterization of neutralizing antibodies and identification of neutralizing epitope mimics on the Clostridium botulinum neurotoxin type A   
• Yang GH et al. 2004: Isolation and characterization of a neutralizing antibody specific to internalization domain of Clostridium botulinum neurotoxin type B

Antitoxin References

• Arnon SS et al. 2006: Human botulism immune globulin for the treatment of infant botulism  
• Hibbs RG et al. 1996: Experience with the use of an investigational F(ab')2 heptavalent botulism immune globulin of equine origin during an outbreak of type E botulism in Egypt
• McLaughlin JB 2004: Botulism type E outbreak associated with eating a beached whale, Alaska  

Epitope References

• Atassi MZ et al. 2005: Submolecular recognition profiles in two mouse strains of non-protective and protective antibodies against botulinum neurotoxin A
• Kondo A et al. 1997: Two distinct HLA-A*0101-specific submotifs illustrate alternative peptide binding modes
• Moreau V et al. 2006: Discontinuous epitope prediction based on mimotope analysis  
• Peters B et al. 2005: The design and implementation of the immune epitope database and analysis resource
• Sathiamurthy M et al. 2005: An ontology for immune epitopes: application to the design of a broad scope database of immune reactivities  
• Wu HC et al. 2001: Characterization of neutralizing antibodies and identification of neutralizing epitope mimics on the Clostridium botulinum neurotoxin type A  

Gene and Strain References

• Anellis A et al. 1972: Production of types A and B spores of Clostridium botulinum by the biphasic method: effect on spore population, radiation resistance, and toxigenicity  
• Binz T et al. 2000: Nucleotide sequence of the gene encoding Clostridium botulinum neurotoxin type D  
• Bhandari M et al. 1997: Molecular characterization of the clusters of genes encoding the botulinum neurotoxin complex in Clostridium botulinum (Clostridium argentinense) type G and nonproteolytic Clostridium botulinum type B
• Campbell K et al. 1993: Nucleotide sequence of the gene coding for Clostridium botulinum (Clostridium argentinense) type G neurotoxin: genealogical comparison with other clostridial neurotoxins
• Dineen SS et al. 2003: Neurotoxin gene clusters in Clostridium botulinum type A strains: sequence comparison and evolutionary implications
• Dineen SS et al. 2000: Cloning, nucleotide sequence, and expression of the gene encoding the bacteriocin boticin B from Clostridium botulinum strain 213B  
• East AK et al. 1998: Analysis of the botulinum neurotoxin type F gene clusters in proteolytic and nonproteolytic Clostridium botulinum and Clostridium barati
• East AK et al. 1996: 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  
• Fujii N et al. 1996: Characterization of component-I gene of botulinum C2 toxin and PCR detection of its gene in clostridial species
• Gessler F 2005: A new scaleable method for the purification of botulinum neurotoxin type E
• Hauser D et al. 1994: Organization of the botulinum neurotoxin C1 gene and its associated non-toxic protein genes in Clostridium botulinum C468
• Hines HB et al. 2005: Characterization of botulinum progenitor toxins by mass spectrometry  
• Hutson RA et al. 1994: Nucleotide sequence of the gene coding for non-proteolytic Clostridium botulinum type B neurotoxin: comparison with other clostridial neurotoxins
• Hyytia E et al. 1999: Characterisation of Clostridium botulinum groups I and II by randomly amplified polymorphic DNA analysis and repetitive element sequence-based PCR
• Kirma N et al. 1998: Characterization of six type A strains of Clostridium botulinum that contain type B toxin gene sequences
• Kouguchi H et al. 2002: In vitro reconstitution of the Clostridium botulinum type D progenitor toxin  
• Moriishi K et al. 1996: Molecular cloning of the gene encoding the mosaic neurotoxin, composed of parts of botulinum neurotoxin types C1 and D, and PCR detection of this gene from Clostridium botulinum type C organisms  
• Moriishi K et al. 1993: Two different types of ADP-ribosyltransferase C3 from Clostridium botulinum type D lysogenized organisms  
• Nakajima H et al. 1998: Molecular composition of the 16S toxin produced by a Clostridium botulinum type D strain, 1873
• Nevas M et al. 2005: Diversity of proteolytic Clostridium botulinum strains, determined by a pulsed-field gel electrophoresis approach  
• Patterson-Curtis SI and Johnson EA 1989: Regulation of neurotoxin and protease formation in Clostridium botulinum Okra B and Hall A by arginine  
• Poulet S et al. 1992: Sequences of the botulinal neurotoxin E derived from Clostridium botulinum type E (strain Beluga) and Clostridium butyricum (strains ATCC 43181 and ATCC 43755)
• Santos-Buelga JA et al. 1998: Characterization of the genes encoding the botulinum neurotoxin complex in a strain of Clostridium botulinum producing type B and F neurotoxins
• Thompson DE et al. 1998: The complete amino acid sequence of the Clostridium botulinum type A neurotoxin, deduced by nucleotide sequence analysis of the encoding gene
• Whelan SM et al. 1992: Molecular cloning of the Clostridium botulinum structural gene encoding the type B neurotoxin and determination of its entire nucleotide sequence  
• Whelan SM et al. 1992: The complete amino acid sequence of the Clostridium botulinum type-E neurotoxin, derived by nucleotide-sequence analysis of the encoding gene
• Willems A et al. 1993: Sequence of the gene coding for the neurotoxin of Clostridium botulinum type A associated with infant botulism: comparison with other clostridial neurotoxins

Infant Botulism References

• FDA: Product Approval Information - Licensing Action on Botulism Immune Globulin Intravenous (Human) (BabyBIG)
• Infant Botulism Treatment & Prevention Program: Infant botulism chapter for inclusion in the Textbook of Pediatric Infectious Disease, fourth edition
  • Introduction
  • History
  • Etiologic Agent
  • Pathogenesis
  • Epidemiology
    • Table 1 Cases and Incidence of Infant Botulism, Top 10 Incidence States, 1977-1995
  • Clinical Manifestations
  • Differential Diagnosis and Diagnosis
    • Table 2 Neurologic Signs Helpful in the Diagnosis of Infant Botulism
    • Table 3 Complications of Infant Botulism
    • Table 4 Working Differential Diagnosis of Infant Botulism
  • Treatment
  • Outcome and Prognosis
  • Prevention
  • Suggested Readings
  • References

Inhibitor References

• Adler M et al. 1998: Efficacy of a novel metalloprotease inhibitor on botulinum neurotoxin B activity
• Anne C et al. 2003: Development of potent inhibitors of botulinum neurotoxin type B
• Boldt GE et al. 2006: Identification of a botulinum neurotoxin A protease inhibitor displaying efficacy in a cellular model   
• Breidenbach MA and Brunger AT 2005: New insights into clostridial neurotoxin-SNARE interactions
• Burnett JC et al. 2005:  The evolving field of biodefence: therapeutic developments and diagnostics  
• Burnett JC et al. 2003: Novel small molecule inhibitors of botulinum neurotoxin A metalloprotease activity
• Cai F et al. 2006: Comparison of extracellular and intracellular potency of botulinum neurotoxins  
• Eswaramoorthy S et al. 2002: A novel mechanism for Clostridium botulinum neurotoxin inhibition
• Ferreira JL et al. 2003: Detection of botulinal neurotoxins A, B, E, and F by amplified enzyme-linked immunosorbent assay: collaborative study
• Keller JE and Neale EA 2001: The role of the synaptic protein snap-25 in the potency of botulinum neurotoxin type A   
• Schmidt JJ and Stafford RG 2005: Botulinum neurotoxin serotype F: identification of substrate recognition requirements and development of inhibitors with low nanomolar affinity
• Schmidt JJ and Stafford RG 2002: A high-affinity competitive inhibitor of type A botulinum neurotoxin protease activity
• Sukonpan C et al. 2004: Synthesis of substrates and inhibitors of botulinum neurotoxin type A metalloprotease

Protocol References

• Adler M et al. 2003: A capillary electrophoresis technique for evaluating botulinum neurotoxin B light chain activity
• Adler M et al. 1999: Promising new approaches for treatment of botulinum intoxication
• Barr JR et al. 2005: Botulinum neurotoxin detection and differentiation by mass spectrometry  
• Caya JG et al. 2004: Clostridium botulinum and the clinical laboratorian: a detailed review of botulism, including biological warfare ramifications of botulinum toxin  
• Goodnough MC et al. 2002: Development of a delivery vehicle for intracellular transport of botulinum neurotoxin antagonists
• Lindstrom M and Korkeala H 2006: Laboratory diagnostics of botulism
• Lewis KH and Hill EV 1947: Practical Media and Control Measures for Producing Highly Toxic Cultures of Clostridium botulinum, Type A  
• Summary of the NIAID expert panel on Botulinum diagnostics 2003  

Research History

• IC Hall:

  • The occurrence of Bacillus botulinus, types A and B, in accidental wounds    (1945)
  • The detection of Bacillus botulinus and Bacillus tetani in soil samples by the constricted tube method    (1924)
  • The effect of certain bacteria upon the toxin production of Bacillus botulinus in vitro    (1923)

• JH Mueller:

  • Glutamine in the production of tetanus toxin    (1949)
  • Growth Requirements of Clostridium tetani    (1942)
  • Studies on cultural requirements of bacteria II    (1922)
  • Studies on cultural requirements of bacteria I    (1922)

• EJ Schantz:

  • Properties and use of botulinum toxin and other microbial neurotoxins in medicine    (1992)
  • Dependence of time to death on molecular size of botulinum toxin    (1970)
  • Amino acid composition of crystalline botulinum toxin, type A    (1967)
  • Observations on the fluorescence and toxicity of botulinum toxin     (1960)

Strain References

• East AK et al. 1996: 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  
• Franciosa G et al. 1994: Detection of type A, B, and E botulism neurotoxin genes in Clostridium botulinum and other Clostridium species by PCR: evidence of unexpressed type B toxin genes in type A toxigenic organisms  
• Smith LD 1975: Inhibition of Clostridium botulinum by strains of Clostridium perfringens isolated from soil  

Structure References

• Agarwal R et al. 2005: Structural analysis of botulinum neurotoxin serotype F light chain: implications on substrate binding and inhibitor design
• Agarwal R et al. 2004:  Structural analysis of botulinum neurotoxin type E catalytic domain and its mutant Glu212-->Gln reveals the pivotal role of the Glu212 carboxylate in the catalytic pathway
• Arndt JW et al. 2005: Crystal structure of botulinum neurotoxin type G light chain: serotype divergence in substrate recognition
• Eswaramoorthy S et al. 2004: Role of metals in the biological activity of Clostridium botulinum neurotoxins
• Inoue K et al. 2003: Structural analysis by X-ray crystallography and calorimetry of a haemagglutinin component (HA1) of the progenitor toxin from Clostridium botulinum  
• Lacy DB et al. 1998: Crystal structure of botulinum neurotoxin type A and implications for toxicity
• Segelke B et al. 2004: Crystal structure of Clostridium botulinum neurotoxin protease in a product-bound state: Evidence for noncanonical zinc protease activity
• Swaminathan S et al. 2000: Structural analysis of the catalytic and binding sites of Clostridium botulinum neurotoxin B

Toxin References

• Abbitt B et al. 1984: Catastrophic death losses in a dairy herd attributed to type D botulism
• Adler M et al. 2001: Persistence of botulinum neurotoxin A demonstrated by sequential administration of serotypes A and E in rat EDL muscle
• Binz T et al. 1990: The complete sequence of botulinum neurotoxin type A and comparison with other clostridial neurotoxins  
• Brett MM et al. 2005: A case of infant botulism with a possible link to infant formula milk powder: evidence for the presence of more than one strain of Clostridium botulinum in clinical specimens and food
• Demarchi J 1958: Existence of type D botulism in man
• Elad D et al. 2004: Natural Clostridium botulinum type C toxicosis in a group of cats  
• Goonetilleke A and Harris JB 2004: Clostridial neurotoxins  
• Green J et al. 1983:  Human botulism (type F) -- a rare type
• Hines HB et al. 2005: Characterization of botulinum progenitor toxins by mass spectrometry  
• Hyytia E et al. 1999: Characterisation of Clostridium botulinum groups I and II by randomly amplified polymorphic DNA analysis and repetitive element sequence-based PCR
• Kalluri P et al. 2003: An outbreak of foodborne botulism associated with food sold at a salvage store in Texas  
• Keller JE et al. 1999: Persistence of botulinum neurotoxin action in cultured spinal cord cells
• McLaughlin JB 2004: Botulism type E outbreak associated with eating a beached whale, Alaska  
• Oguma K et al. 1990: Infant botulism due to Clostridium botulinum type C toxin
• Schantz E et al. 1960: Observations on the fluorescence and toxicity of botulinum toxin  
• Schiavo G et al. 1994: Botulinum G neurotoxin cleaves VAMP/synaptobrevin at a single Ala-Ala peptide bond  
• Shapiro RL et al. 1998: Botulism in the United States: a clinical and epidemiologic review
• Smith TJ et al. 2005: Sequence variation within botulinum neurotoxin serotypes impacts antibody binding and neutralization  
• Sonnabend O et al. 1981:  Isolation of Clostridium botulinum type G and identification of type G botulinal toxin in humans: report of five sudden unexpected deaths
• Stefanye D et al. 1967: Amino acid composition of crystalline botulinum toxin, type A  
• Telzak EE et al. 1990: An international outbreak of type E botulism due to uneviscerated fish

Vaccine References

• Byrne MP and Smith LA 2000: Development of vaccines for prevention of botulism
• Clayton J and Middlebrook JL 2000: Vaccination of mice with DNA encoding a large fragment of botulinum neurotoxin serotype A
• Clayton MA et al. 1995: Protective vaccination with a recombinant fragment of Clostridium botulinum neurotoxin serotype A expressed from a synthetic gene in Escherichia coli  
• Dertzbaugh MT and West MW 1996: Mapping of protective and cross-reactive domains of the type A neurotoxin of Clostridium botulinum
• Kobayashi R et al. 2005: A novel neurotoxoid vaccine prevents mucosal botulism  
• Lee JS et al. 2001: Candidate vaccine against botulinum neurotoxin serotype A derived from a Venezuelan equine encephalitis virus vector system  
• Shyu RH et al. 2000: DNA vaccination using the fragment C of botulinum neurotoxin type A provided protective immunity in mice