Skip to main content

Complexity of Botulinum Neurotoxins: Challenges for Detection Technology

  • Chapter
  • First Online:
Botulinum Neurotoxins

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

Abstract

The detection of botulinum neurotoxins (BoNT) is extremely challenging due to their high toxicity and the multiple BoNT variants. To date, seven serotypes with more than 30 subtypes have been described, and even more subtypes are expected to be discovered. The fact that the BoNT molecules are released as large complexes of different size and composition adds further complexity to the issue. Currently, in the diagnostics of botulism, the mouse bioassay (MBA) is still considered as gold standard for the detection of BoNT in complex sample materials. Over the years, different functional, immunological, and spectrometric assays or combinations thereof have been developed, supplemented by DNA-based assays for the detection of the organism. In this review, advantages and limitations of the current technologies will be discussed, highlighting some of the intricacies of real sample analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ALISSA:

Assay using a large immuno-sorbent surface area

BoNT:

Botulinum neurotoxin

ELISA:

Enzyme-linked immunosorbent assay

ESI:

Electrospray ionization

FRET:

Förster resonance energy transfer

GE:

Genome equivalents

HA:

Hemagglutinin

HC:

Heavy chain

LC:

Light chain

LC:

Liquid chromatography

LFA:

Lateral flow assay

mAb:

Monoclonal antibody

MALDI:

Matrix-assisted laser desorption/ionization

MBA:

Mouse bioassay

MPN ASSAY :

Mouse phrenic nerve hemidiaphragm assay

MS:

Mass spectrometry

NTNHA:

Non-toxic nonhemagglutinin

orf:

Open reading frame

pAb:

Polyclonal antibody

PCR:

Polymerase chain reaction

PTC:

Progenitor toxin complex

SNAP-25:

Synaptosome-associated protein of 25 kDa

SNARE:

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor

TeNT:

Tetanus neurotoxin

TOF:

Time-of-flight

VAMP:

Vesicle-associated membrane protein

References

  • Adler M, Wacker R, Niemeyer CM (2008) Sensitivity by combination: immuno-PCR and related technologies. Analyst 133:702–718

    Article  CAS  PubMed  Google Scholar 

  • Akbulut D, Grant KA, McLauchlin J (2004) Development and application of real-time PCR assays to detect fragments of the Clostridium botulinum types A, B, and E neurotoxin genes for investigation of human foodborne and infant botulism. Foodborne Pathog Dis 1:247–257

    Article  CAS  PubMed  Google Scholar 

  • Aktories K, Lang AE, Schwan C et al (2011) Actin as target for modification by bacterial protein toxins. FEBS J 278:4526–4543

    Article  CAS  PubMed  Google Scholar 

  • Anderson GP, Taitt CR (2008) Amplification of microsphere-based microarrays using catalyzed reporter deposition. Biosens Bioelectron 24:324–328

    Article  CAS  PubMed  Google Scholar 

  • Anne C, Cornille F, Lenoir C et al (2001) High-throughput fluorogenic assay for determination of botulinum type B neurotoxin protease activity. Anal Biochem 291:253–261

    Article  CAS  PubMed  Google Scholar 

  • Anniballi F, Auricchio B, Delibato E et al (2012) Multiplex real-time PCR SYBR green for detection and typing of group III Clostridium botulinum. Vet Microbiol 154:332–338

    Article  CAS  PubMed  Google Scholar 

  • Ahnert-Hilger G, Münster-Wandowski A, Höltje M (2012) Synaptic vesicle proteins: Targets and routes for Botulinum nurotoxins. doi:10.1007/978-3-642-33570-9-8

  • Aoki KR (2001) A comparison of the safety margins of botulinum neurotoxin serotypes A, B, and F in mice. Toxicon 39:1815–1820

    Article  CAS  PubMed  Google Scholar 

  • Aranda E, Rodriguez MM, Asensio MA et al (1997) Detection of Clostridium botulinum types A, B, E and F in foods by PCR and DNA probe. Lett Appl Microbiol 25:186–190

    Article  CAS  PubMed  Google Scholar 

  • Arnon SS, Schechter R, Inglesby TV et al (2001) Botulinum toxin as a biological weapon: medical and public health management. J Am Med Assoc 285:1059–1070

    Article  CAS  Google Scholar 

  • Artin I, Bjorkman P, Cronqvist J et al (2007) First case of type E wound botulism diagnosed using real-time PCR. J Clin Microbiol 45:3589–3594

    Article  CAS  PubMed  Google Scholar 

  • Attrée O, Guglielmo-Viret V, Gros V et al (2007) Development and comparison of two immunoassay formats for rapid detection of botulinum neurotoxin type A. J Immunol Methods 325:78–87

    Article  PubMed  CAS  Google Scholar 

  • Bagramyan K, Kalkum M (2011) Ultrasensitive detection of botulinum neurotoxins and anthrax lethal factor in biological samples by ALISSA. Methods Mol Biol 739:23–36

    Article  CAS  PubMed  Google Scholar 

  • Bagramyan K, Barash JR, Arnon SS et al (2008) Attomolar detection of botulinum toxin type A in complex biological matrices. PLoS ONE 3:e2041

    Article  PubMed  CAS  Google Scholar 

  • Balsam J, Ossandon M, Kostov Y et al (2011) Lensless CCD-based fluorometer using a micromachined optical Söller collimator. Lab Chip 11:941–949

    Article  CAS  PubMed  Google Scholar 

  • Barr JR, Moura H, Boyer AE et al (2005) Botulinum neurotoxin detection and differentiation by mass spectrometry. Emerg Infect Dis 11:1578–1583

    Article  CAS  PubMed  Google Scholar 

  • Bengtson I (1921) Direct inoculation test for B. botulinus toxin. Public Health Rep 36:1665–1671

    Article  Google Scholar 

  • Bengtson I (1922) Preliminary note on a toxin-producing anaerobe isolated from the larvae of Lucilia caesar. Public Health Rep 37:164–170

    Article  Google Scholar 

  • Bercsenyi k, Giribaldi F, Schiavo G (2012) The elusive compass of clostridial Neurotoxins: Deciding when and where to go. doi:10.1007/978-3-642-33570-9-5

  • Betley MJ, Sugiyama H (1979) Noncorrelation between mouse toxicity and serologically assayed toxin in Clostridium botulinum type A culture fluids. Appl Environ Microbiol 38:297–300

    CAS  PubMed  Google Scholar 

  • Binz T (2012) Clostridial Neurotoxin light chains:Devices for SNARE cleavage Mediated blockde of neurotransmission. doi:10.1007/978-3-642-33570-9-7

  • Boyer AE, Moura H, Woolfitt AR et al (2005) From the mouse to the mass spectrometer: detection and differentiation of the endoproteinase activities of botulinum neurotoxins A–G by mass spectrometry. Anal Chem 77:3916–3924

    Article  CAS  PubMed  Google Scholar 

  • Boyer AE, Gallegos-Candela M, Lins RC et al (2011) Quantitative mass spectrometry for bacterial protein toxins—a sensitive, specific, high-throughput tool for detection and diagnosis. Molecules 16:2391–2413

    Article  CAS  PubMed  Google Scholar 

  • Braconnier A, Broussolle V, Perelle S et al (2001) Screening for Clostridium botulinum type A, B, and E in cooked chilled foods containing vegetables and raw material using polymerase chain reaction and molecular probes. J Food Prot 64:201–207

    CAS  PubMed  Google Scholar 

  • Breidenbach MA, Brunger AT (2004) Substrate recognition strategy for botulinum neurotoxin serotype A. Nature 432:925–929

    Article  CAS  PubMed  Google Scholar 

  • Brooks CE, Clarke HJ, Finlay DA et al (2010) Culture enrichment assists the diagnosis of cattle botulism by a monoclonal antibody based sandwich ELISA. Vet Microbiol 144:226–230

    Article  CAS  PubMed  Google Scholar 

  • Brunger AT, Rummel A (2009) Receptor and substrate interactions of clostridial neurotoxins. Toxicon 54:550–560

    Article  CAS  PubMed  Google Scholar 

  • Brunger AT, Jin R, Breidenbach MA (2008) Highly specific interactions between botulinum neurotoxins and synaptic vesicle proteins. Cell Mol Life Sci 65:2296–2306

    Article  CAS  PubMed  Google Scholar 

  • Brunt J, Webb MD, Peck MW (2010) Rapid affinity immunochromatography column-based tests for sensitive detection of Clostridium botulinum neurotoxins and Escherichia coli O157. Appl Environ Microbiol 76:4143–4150

    Article  CAS  PubMed  Google Scholar 

  • Burgen ASV, Dickens F, Zatman LJ (1949) The action of botulinum toxin on the neuro-muscular junction. J Physiol 109:10–24

    CAS  PubMed  Google Scholar 

  • Chao H-Y, Wang Y-C, Tang S-S et al (2004) A highly sensitive immuno-polymerase chain reaction assay for Clostridium botulinum neurotoxin type A. Toxicon 43:27–34

    Article  CAS  PubMed  Google Scholar 

  • Chiao DJ, Shyu RH, Hu CS et al (2004) Colloidal gold-based immunochromatographic assay for detection of botulinum neurotoxin type B. J Chromatogr B Analyt Technol Biomed Life Sci 809:37–41

    Article  CAS  PubMed  Google Scholar 

  • Chiao DJ, Wey JJ, Shyu RH et al (2008a) Monoclonal antibody-based lateral flow assay for detection of botulinum neurotoxin type A. Hybridoma (Larchmt) 27:31–35

    Article  CAS  Google Scholar 

  • Chiao DJ, Wey JJ, Tang SS (2008b) Monoclonal antibody-based enzyme immunoassay for detection of botulinum neurotoxin type A. Hybridoma (Larchmt) 27:43–47

    Article  CAS  Google Scholar 

  • Collins MD, East AK (1998) Phylogeny and taxonomy of the food-borne pathogen Clostridium botulinum and its neurotoxins. J Appl Microbiol 84:5–17

    Article  CAS  PubMed  Google Scholar 

  • Craven KE, Ferreira JL, Harrison MA et al (2002) Specific detection of Clostridium botulinum types A, B, E, and F using the polymerase chain reaction. J AOAC Int 85:1025–1028

    CAS  PubMed  Google Scholar 

  • De Medici D, Anniballi F, Wyatt GM et al (2009) Multiplex PCR to detect botulinum neurotoxin-producing clostridia in clinical, food and environmental samples. Appl Environ Microbiol 75:6457–6461

    Article  PubMed  CAS  Google Scholar 

  • Dezfulian M, Hatheway CL, Yolken RH et al (1984) Enzyme-linked immunosorbent assay for detection of Clostridium botulinum type A and type B toxins in stool samples of infants with botulism. J Clin Microbiol 20:379–383

    CAS  PubMed  Google Scholar 

  • Doellgast GJ, Triscott MX, Beard GA et al (1993) Sensitive enzyme-linked immunosorbent assay for detection of Clostridium botulinum neurotoxins A, B, and E using signal amplification via enzyme-linked coagulation assay. J Clin Microbiol 31:2402–2409

    CAS  PubMed  Google Scholar 

  • Doellgast GJ, Beard GA, Bottoms JD et al (1994) Enzyme-linked immunosorbent assay and enzyme-linked coagulation assay for detection of Clostridium botulinum neurotoxins A, B, and E and solution-phase complexes with dual-label antibodies. J Clin Microbiol 32:105–111

    CAS  PubMed  Google Scholar 

  • Dong M, Tepp WH, Johnson EA et al (2004) Using fluorescent sensors to detect botulinum neurotoxin activity in vitro and in living cells. Proc Natl Acad Sci U S A 101:14701–14706

    Article  CAS  PubMed  Google Scholar 

  • Dorner BG, Steinbach S, Hüser MB et al (2003) Single-cell analysis of the murine chemokines MIP-1alpha, MIP-1beta, RANTES and ATAC/lymphotactin by flow cytometry. J Immunol Methods 274:83–91

    Article  CAS  PubMed  Google Scholar 

  • Dressler D, Lange M, Bigalke H (2005) Mouse diaphragm assay for detection of antibodies against botulinum toxin type B. Mov Disord 20:1617–1619

    Article  PubMed  Google Scholar 

  • East AK, Collins MD (1994) Conserved structure of genes encoding components of botulinum neurotoxin complex M and the sequence of the gene coding for the nontoxic component in nonproteolytic Clostridium botulinum type F. Curr Microbiol 29:69–77

    Article  CAS  PubMed  Google Scholar 

  • Ekong TAN, McLellan K, Sesardic D (1995) Immunological detection of Clostridium botulinum toxin type A in therapeutic preparations. J Immunol Methods 180:181–191

    Article  CAS  PubMed  Google Scholar 

  • Evans ER, Skipper PJ, Shone CC (2009) An assay for botulinum toxin types A, B and F that requires both functional binding and catalytic activities within the neurotoxin. J Appl Microbiol 107:1384–1391

    Article  CAS  PubMed  Google Scholar 

  • Fach P, Gibert M, Griffais R et al (1995) PCR and gene probe identification of botulinum neurotoxin A-, B-, E-, F-, and G-producing Clostridium spp. and evaluation in food samples. Appl Environ Microbiol 61:389–392

    CAS  PubMed  Google Scholar 

  • Fach P, Micheau P, Mazuet C et al (2009) Development of real-time PCR tests for detecting botulinum neurotoxins A, B, E, F producing Clostridium botulinum, Clostridium baratii and Clostridium butyricum. J Appl Microbiol 107:465–473

    Article  CAS  PubMed  Google Scholar 

  • Fach P, Fenicia L, Knutsson R et al (2011) An innovative molecular detection tool for tracking and tracing Clostridium botulinum types A, B, E, F and other botulinum neurotoxin producing Clostridia based on the GeneDisc cycler. Int J Food Microbiol 145:S145–S151

    Article  CAS  PubMed  Google Scholar 

  • Fenicia L, Anniballi F, De MD et al (2007) SYBR green real-time PCR method to detect Clostridium botulinum type A. Appl Environ Microbiol 73:2891–2896

    Article  CAS  PubMed  Google Scholar 

  • Fenicia L, Fach P, van Rotterdam BJ et al (2011) Towards an international standard for detection and typing botulinum neurotoxin-producing Clostridia types A, B, E and F in food, feed and environmental samples: a European ring trial study to evaluate a real-time PCR assay. Int J Food Microbiol 145:S152–S157

    Article  PubMed  Google Scholar 

  • Ferracci G, Marconi S, Mazuet C et al (2011) A label-free biosensor assay for botulinum neurotoxin B in food and human serum. Anal Biochem 410:281–288

    Article  CAS  PubMed  Google Scholar 

  • Ferreira JL (2001) Comparison of amplified ELISA and mouse bioassay procedures for determination of botulinal toxins A, B, E, and F. J AOAC Int 84:85–88

    CAS  PubMed  Google Scholar 

  • Ferreira JL, Hamdy MK, Herd ZL et al (1987) Monoclonal antibody for the detection of Clostridium botulinum type A toxin. Mol Cell Probes 1:337–345

    Article  CAS  PubMed  Google Scholar 

  • Ferreira JL, Hamdy MK, McCay SG et al (1990) Monoclonal antibody to type F Clostridium botulinum toxin. Appl Environ Microbiol 56:808–811

    CAS  PubMed  Google Scholar 

  • Ferreira JL, Eliasberg SJ, Harrison MA et al (2001) Detection of preformed type A botulinal toxin in hash brown potatoes by using the mouse bioasssay and a modified ELISA test. J AOAC Int 84:1460–1464

    CAS  PubMed  Google Scholar 

  • Ferreira JL, Maslanka S, Johnson E et al (2003) Detection of botulinal neurotoxins A, B, E, and F by amplified enzyme-linked immunosorbent assay: collaborative study. J AOAC Int 86:314–331

    CAS  PubMed  Google Scholar 

  • Ferreira JL, Eliasberg SJ, Edmonds P et al (2004) Comparison of the mouse bioassay and enzyme-linked immunosorbent assay procedures for the detection of type A botulinal toxin in food. J Food Prot 67:203–206

    CAS  PubMed  Google Scholar 

  • Fischer A (2012) Synchronized Chapterone function of Botulinum neurotoxin domain Mediates light chain translocation into neutrons.doi:10.1007/978-3-642-33570-9-6

  • Förster T (1948) Zwischenmolekulare Energiewanderung und Fluoreszenz. Ann Phys 437:55–75

    Article  Google Scholar 

  • Franciosa G, Ferreira JL, Hatheway CL (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. J Clin Microbiol 32:1911–1917

    CAS  PubMed  Google Scholar 

  • Franciosa G, Fenicia L, Caldiani C et al (1996) PCR for detection of Clostridium botulinum type C in avian and environmental samples. J Clin Microbiol 34:882–885

    CAS  PubMed  Google Scholar 

  • Fujinaga Y (2006) Transport of bacterial toxins into target cells: pathways followed by cholera toxin and botulinum progenitor toxin. J Biochem 140:155–160

    Article  CAS  PubMed  Google Scholar 

  • Fujinaga Y (2010) Interaction of botulinum toxin with the epithelial barrier. J Biomed Biotechnol 2010:974943

    Article  PubMed  CAS  Google Scholar 

  • Fujinaga Y, Inoue K, Shimazaki S et al (1994) Molecular construction of Clostridium botulinum type C progenitor toxin and its gene organization. Biochem Biophys Res Commun 205:1291–1298

    Article  CAS  PubMed  Google Scholar 

  • Fujinaga Y, Matsumura T, Jin Y et al (2009) A novel function of botulinum toxin-associated proteins: HA proteins disrupt intestinal epithelial barrier to increase toxin absorption. Toxicon 54:583–586

    Article  CAS  PubMed  Google Scholar 

  • Fujinaga Y, Sugawara Y,Mtsumura T (2012) Uptake of Botulinum Neurotoxin in the intestine.doi: 10.1007/978-3-642-33570-9-3

  • Ganapathy R, Padmanabhan S, Eric YP et al (2008) Rapid detection of botulinum neurotoxins A, B, E, and F by optical immunoassay. Front Biosci 13:5432–5440

    Article  CAS  PubMed  Google Scholar 

  • Garber EA, Venkateswaran KV, O’Brien TW (2010) Simultaneous multiplex detection and confirmation of the proteinaceous toxins abrin, ricin, botulinum toxins, and Staphylococcus enterotoxins A, B, and C in food. J Agric Food Chem 58:6600–6607

    Article  CAS  PubMed  Google Scholar 

  • Gaunt PS, Kalb SR, Barr JR (2007) Detection of botulinum type E toxin in channel catfish with visceral toxicosis syndrome using catfish bioassay and endopep mass spectrometry. J Vet Diagn Invest 19:349–354

    Article  PubMed  Google Scholar 

  • Gauthier M, Cadieux B, Austin JW et al (2005) Cloth-based hybridization array system for the detection of Clostridium botulinum type A, B, E, and F neurotoxin genes. J Food Prot 68:1477–1483

    CAS  PubMed  Google Scholar 

  • Gessler F, Hampe K, Böhnel H (2005) Sensitive detection of botulinum neurotoxin types C and D with an immunoaffinity chromatographic column test. Appl Environ Microbiol 71:7897–7903

    Article  CAS  PubMed  Google Scholar 

  • Gessler F, Hampe K, Schmidt M et al (2006) Immunomagnetic beads assay for the detection of botulinum neurotoxin types C and D. Diagn Microbiol Infect Dis 56:225–232

    Article  CAS  PubMed  Google Scholar 

  • Gessler F, Pagel-Wieder S, Avondet MA et al (2007) Evaluation of lateral flow assays for the detection of botulinum neurotoxin type A and their application in laboratory diagnosis of botulism. Diagn Microbiol Infect Dis 57:243–249

    Article  CAS  PubMed  Google Scholar 

  • Gibson AM, Modi NK, Roberts TA et al (1987) Evaluation of a monoclonal antibody-based immunoassay for detecting type A Clostridium botulinum toxin produced in pure culture and an inoculated model cured meat system. J Appl Bacteriol 63:217–226

    Article  CAS  PubMed  Google Scholar 

  • Gibson AM, Modi NK, Roberts TA et al (1988) Evaluation of a monoclonal antibody-based immunoassay for detecting type B Clostridium botulinum toxin produced in pure culture and an inoculated model cured meat system. J Appl Bacteriol 64:285–291

    Article  CAS  PubMed  Google Scholar 

  • Gilmore MA, Williams D, Okawa Y et al (2011) Depolarization after resonance energy transfer (DARET): a sensitive fluorescence-based assay for botulinum neurotoxin protease activity. Anal Biochem 413:36–42

    Article  CAS  PubMed  Google Scholar 

  • Giménez DF, Cicarelli AS (1970) Studies on strain 84 of Clostridium botulinum. Zentralbl Bakteriol Parasitenkd Infektionskr Abt 1 Orig Reihe A 215:212–220

    Google Scholar 

  • Grate JW, Warner MG, Ozanich RM Jr et al (2009) Renewable surface fluorescence sandwich immunoassay biosensor for rapid sensitive botulinum toxin detection in an automated fluidic format. Analyst 134:987–996

    Article  CAS  PubMed  Google Scholar 

  • Gu S, Rumpel S, Zhou J et al (2012) Botulinum neurotoxin is shielded by NTNHA in an interlocked complex. Science 335:977–981

    Article  CAS  PubMed  Google Scholar 

  • Gu S, Jin R (2012) Assembly and function of the Botulinum neurotoxin progenitor complex. doi: 10.1007/978-3-642-33570-9-2

  • Guglielmo-Viret V, Attree O, Blanco-Gros V et al (2005) Comparison of electrochemiluminescence assay and ELISA for the detection of Clostridium botulinum type B neurotoxin. J Immunol Methods 301:164–172

    Article  CAS  PubMed  Google Scholar 

  • Gunnison JB, Cummings JR, Meyer KF (1936) Clostridium botulinum Type E. Proc Soc Exp Biol Med 35:278–280

    Google Scholar 

  • Habermann E, Dreyer F, Bigalke H (1980) Tetanus toxin blocks the neuromuscular transmission in vitro like botulinum A toxin. Naunyn Schmiedebergs Arch Pharmacol 311:33–40

    Article  CAS  PubMed  Google Scholar 

  • Hallis B, James BA, Shone CC (1996) Development of novel assays for botulinum type A and B neurotoxins based on their endopeptidase activities. J Clin Microbiol 34:1934–1938

    CAS  PubMed  Google Scholar 

  • Han SM, Cho JH, Cho IH et al (2007) Plastic enzyme-linked immunosorbent assays (ELISA)-on-a-chip biosensor for botulinum neurotoxin A. Anal Chim Acta 587:1–8

    Article  CAS  PubMed  Google Scholar 

  • Hasegawa K, Watanabe T, Suzuki T et al (2007) A novel subunit structure of Clostridium botulinum serotype D toxin complex with three extended arms. J Biol Chem 282:24777–24783

    Article  CAS  PubMed  Google Scholar 

  • Hatheway CL, McCroskey LM (1987) Examination of feces and serum for diagnosis of infant botulism in 336 patients. J Clin Microbiol 25:2334–2338

    CAS  PubMed  Google Scholar 

  • Hazen EL (1937) A strain of B. botulinus not classified as type A, B, or C. J Infect Dis 60:260–264

    Article  Google Scholar 

  • Hedeland M, Moura H, Baverud V et al (2011) Confirmation of botulism in birds and cattle by the mouse bioassay and Endopep-MS. J Med Microbiol 60:1299–1305

    Article  CAS  PubMed  Google Scholar 

  • Heffron A, Poxton IR (2007) A PCR approach to determine the distribution of toxin genes in closely related Clostridium species: Clostridium botulinum type C and D neurotoxins and C2 toxin, and Clostridium novyi α toxin. J Med Microbiol 56:196–201

    Article  CAS  PubMed  Google Scholar 

  • Henkel JS, Jacobson M, Tepp W et al (2009) Catalytic properties of botulinum neurotoxin subtypes A3 and A4. Biochemistry 48:2522–2528

    Article  CAS  PubMed  Google Scholar 

  • Hill KK, Smith TJ, Helma CH et al (2007) Genetic diversity among botulinum neurotoxin-producing clostridial strains. J Bacteriol 189:818–832

    Article  CAS  PubMed  Google Scholar 

  • Hill KK, Smith TJ (2012) Genetic diversity within Clostridium botulinum serotypes, botulinum neurotoxin Gene. Cluster and toxin subtypes. doi: 10.1007/978-3-642-33570-9-1

  • Hill BJ, Skerry JC, Smith TJ et al (2010) Universal and specific quantitative detection of botulinum neurotoxin genes. BMC Microbiol 10:267

    Article  PubMed  CAS  Google Scholar 

  • Hines HB, Lebeda F, Hale M et al (2005) Characterization of botulinum progenitor toxins by mass spectrometry. Appl Environ Microbiol 71:4478–4486

    Article  CAS  PubMed  Google Scholar 

  • Huber A, France RM, Riccalton-Banks L et al (2008) The intercostal NMJ assay: a new alternative to the conventional LD50 assay for the determination of the therapeutic potency of botulinum toxin preparations. Altern Lab Anim 36:141–152

    CAS  PubMed  Google Scholar 

  • Inoue K, Fujinaga Y, Watanabe T et al (1996) Molecular composition of Clostridium botulinum type A progenitor toxins. Infect Immun 64:1589–1594

    CAS  PubMed  Google Scholar 

  • Jahn R, Niemann H (1994) Molecular mechanisms of clostridial neurotoxins. Ann N Y Acad Sci 733:245–255

    Article  CAS  PubMed  Google Scholar 

  • Johnson EA, Montecucco C (2008) Botulism. Handb Clin Neurol 91:333–368

    Article  PubMed  Google Scholar 

  • Jones RG, Alsop TA, Hull R et al (2006) Botulinum type A toxin neutralisation by specific IgG and its fragments: a comparison of mouse systemic toxicity and local flaccid paralysis assays. Toxicon 48:246–254

    Article  CAS  PubMed  Google Scholar 

  • Jones RG, Ochiai M, Liu Y et al (2008) Development of improved SNAP25 endopeptidase immuno-assays for botulinum type A and E toxins. J Immunol Methods 329:92–101

    Article  CAS  PubMed  Google Scholar 

  • Jones RG, Liu Y, Sesardic D (2009) New highly specific botulinum type C1 endopeptidase immunoassays utilising SNAP25 or syntaxin substrates. J Immunol Methods 343:21–27

    Article  CAS  PubMed  Google Scholar 

  • Jones RG, Liu Y, Halls C et al (2011) Release of proteolytic activity following reduction in therapeutic human serum albumin containing products: detection with a new neoepitope endopeptidase immunoassay. J Pharm Biomed Anal 54:74–80

    Article  CAS  PubMed  Google Scholar 

  • Joshi SG (2012) Detection of biologically active botulinum neurotoxin-A in serum using high-throughput FRET-assay. J Pharmacol Toxicol Methods 65:8–12

    Article  CAS  PubMed  Google Scholar 

  • Just I, Rohrbeck A, Hülsenbeck SC et al (2011) Therapeutic effects of Clostridium botulinum C3 exoenzyme. Naunyn Schmiedebergs Arch Pharmacol 383:247–252

    Article  CAS  PubMed  Google Scholar 

  • Kalb SR, Goodnough MC, Malizio CJ et al (2005) Detection of botulinum neurotoxin A in a spiked milk sample with subtype identification through toxin proteomics. Anal Chem 77:6140–6146

    Article  CAS  PubMed  Google Scholar 

  • Kalb SR, Moura H, Boyer AE et al (2006) The use of endopep-MS for the detection of botulinum toxins A, B, E, and F in serum and stool samples. Anal Biochem 351:84–92

    Article  CAS  PubMed  Google Scholar 

  • Kalb SR, Smith TJ, Moura H et al (2008) The use of endopep-MS to detect multiple subtypes of botulinum neurotoxins A, B, E, and F. Int J Mass Spectrom 278:101–108

    Article  CAS  Google Scholar 

  • Kalb SR, Lou J, Garcia-Rodriguez C et al (2009) Extraction and inhibition of enzymatic activity of botulinum neurotoxins/A1,/A2, and/A3 by a panel of monoclonal anti-BoNT/A antibodies. PLoS ONE 4:e5355

    Article  PubMed  CAS  Google Scholar 

  • Kalb SR, Garcia-Rodriguez C, Lou J et al (2010) Extraction of BoNT/A,/B,/E, and/F with a single, high affinity monoclonal antibody for detection of botulinum neurotoxin by endopep-MS. PLoS ONE 5:e12237

    Article  PubMed  CAS  Google Scholar 

  • Kalb SR, Pirkle JL, Barr JR (2011a) Mass spectrometric detection of botulinum neurotoxin by measuring its activity in serum and milk. In: Banoub J (ed) Detection of biological agents for the prevention of bioterrorism. Springer, Dordrecht, pp 115–129

    Chapter  Google Scholar 

  • Kalb SR, Santana WI, Geren IN et al (2011b) Extraction and inhibition of enzymatic activity of botulinum neurotoxins/B1,/B2,/B3,/B4, and/B5 by a panel of monoclonal anti-BoNT/B antibodies. BMC Biochem 12:58

    Article  CAS  PubMed  Google Scholar 

  • Kalb SR, Baudys J, Rees JC et al (2012a) De novo subtype and strain identification of botulinum neurotoxin type B through toxin proteomics. Anal Bioanal Chem 403:215–226

    Article  CAS  PubMed  Google Scholar 

  • Kalb SR, Baudys J, Webb RP et al (2012b) Discovery of a novel enzymatic cleavage site for botulinum neurotoxin F5. FEBS Lett 586:109–115

    Article  CAS  PubMed  Google Scholar 

  • Kautter DA, Solomon HM (1977) Collaborative study of a method for the detection of Clostridium botulinum and its toxins in foods. J Assoc Off Anal Chem 60:541–545

    CAS  PubMed  Google Scholar 

  • Keller JE, Neale EA, Oyler G et al (1999a) Persistence of botulinum neurotoxin action in cultured spinal cord cells. FEBS Lett 456:137–142

    Article  CAS  PubMed  Google Scholar 

  • Keller JE, Nowakowski JL, Filbert MG et al (1999b) Rapid microplate assay for monitoring botulinum neurotoxin B catalytic activity. J Appl Toxicol 19:S13–S17

    Article  CAS  PubMed  Google Scholar 

  • Kimura B, Kawasaki S, Nakano H et al (2001) Rapid, quantitative PCR monitoring of growth of Clostridium botulinum type E in modified-atmosphere-packaged fish. Appl Environ Microbiol 67:206–216

    Article  CAS  PubMed  Google Scholar 

  • Kirchner S, Krämer KM, Schulze M et al (2010) Pentaplexed quantitative real-time PCR assay for the simultaneous detection and quantification of botulinum neurotoxin-producing clostridia in food and clinical samples. Appl Environ Microbiol 76:4387–4395

    Article  CAS  PubMed  Google Scholar 

  • Klaubert B, Vujtovic-Ockenga N, Wermter R et al (2009) Determination of botulinum toxins after peptic sample pre-treatment by multidimensional nanoscale liquid chromatography and nano-electrospray ion-trap mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 877:1084–1092

    Article  CAS  PubMed  Google Scholar 

  • Klewitz T, Gessler F, Beer H et al (2006) Immunochromatographic assay for determination of botulinum neurotoxin type D. Sens Actuators B Chem 113:582–589

    Article  CAS  Google Scholar 

  • Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497

    Article  PubMed  Google Scholar 

  • König K, Ringe H, Dorner BG et al (2007) Atypical tetanus in a completely immunized 14-year-old boy. Pediatrics 120:e1355–e1358

    Article  PubMed  Google Scholar 

  • Koriazova LK, Montal M (2003) Translocation of botulinum neurotoxin light chain protease through the heavy chain channel. Nat Struct Biol 10:13–18

    Article  CAS  PubMed  Google Scholar 

  • Kostov Y, Sergeev N, Wilson S et al (2009) A simple portable electroluminescence illumination-based CCD detector. Methods Mol Biol 503:259–272

    Article  CAS  PubMed  Google Scholar 

  • Kozaki S, Miyazaki S, Sakaguchi G (1977) Development of antitoxin with each of two complementary fragments of Clostridium botulinum type B derivative toxin. Infect Immun 18:761–766

    CAS  PubMed  Google Scholar 

  • Kozaki S, Dufrenne J, Hagenaars AM et al (1979) Enzyme linked immunosorbent assay (ELISA) for detection of Clostridium botulinum type B toxin. Jpn J Med Sci Biol 32:199–205

    CAS  PubMed  Google Scholar 

  • Kull S, Pauly D, Störmann B et al (2010) Multiplex detection of microbial and plant toxins by immunoaffinity enrichment and matrix-assisted laser desorption/ionization mass spectrometry. Anal Chem 82:2916–2924

    Article  CAS  PubMed  Google Scholar 

  • Kumar P, Colston JT, Chambers JP et al (1994) Detection of botulinum toxin using an evanescent wave immunosensor. Biosens Bioelectron 9:57–63

    Article  CAS  PubMed  Google Scholar 

  • Ladd J, Taylor AD, Homola J et al (2008) Detection of botulinum neurotoxins in buffer and honey using a surface plasmon resonance (SPR) sensor. Sens Actuators B Chem 130:129–134

    Article  CAS  Google Scholar 

  • Landmann G (1904) Ueber die Ursache der Darmstädter Bohnenvergiftung. Hyg Rundsch 14:449–452

    Google Scholar 

  • Lee JK, Yang KH (1982) Enzyme-linked immunosorbent assay (ELISA) for detection of Clostridium type F toxin. Kor J Appl Microbiol Bioeng 10:205–209

    Google Scholar 

  • Leuchs J (1910) Beiträge zur Kenntnis des toxins und antitoxins des Bacillus botulinus. Z Hyg 65:55–84

    Article  Google Scholar 

  • Lewis GE Jr, Kulinski SS, Reichard DW et al (1981) Detection of Clostridium botulinum type G toxin by enzyme-linked immunosorbent assay. Appl Environ Microbiol 42:1018–1022

    CAS  PubMed  Google Scholar 

  • Lin G, Tepp WH, Pier CL et al (2010) Expression of the Clostridium botulinum A2 neurotoxin gene cluster proteins and characterization of the A2 complex. Appl Environ Microbiol 76:40–47

    Article  CAS  PubMed  Google Scholar 

  • Lindberg A, Skarin H, Knutsson R et al (2010) Real-time PCR for Clostridium botulinum type C neurotoxin (BoNTC) gene, also covering a chimeric C/D sequence-application on outbreaks of botulism in poultry. Vet Microbiol 146:118–123

    Article  CAS  PubMed  Google Scholar 

  • Lindström M, Korkeala H (2006) Laboratory diagnostics of botulism. Clin Microbiol Rev 19:298–314

    Article  PubMed  CAS  Google Scholar 

  • Lindström M, Keto R, Markkula A et al (2001) Multiplex PCR assay for detection and identification of Clostridium botulinum types A, B, E, and F in food and fecal material. Appl Environ Microbiol 67:5694–5699

    Article  PubMed  CAS  Google Scholar 

  • Liu YY, Rigsby P, Sesardic D et al (2012) A functional dual-coated (FDC) microtiter plate method to replace the botulinum toxin LD(50) test. Anal Biochem 425:28–35

    Article  CAS  PubMed  Google Scholar 

  • Lúquez C, Raphael BH, Maslanka SE (2009) Neurotoxin gene clusters in Clostridium botulinum type Ab strains. Appl Environ Microbiol 75:6094–6101

    Article  PubMed  CAS  Google Scholar 

  • Macdonald TE, Helma CH, Shou Y et al (2011) Analysis of Clostridium botulinum serotype E strains by using multilocus sequence typing, amplified fragment length polymorphism, variable-number tandem-repeat analysis, and botulinum neurotoxin gene sequencing. Appl Environ Microbiol 77:8625–8634

    Article  CAS  PubMed  Google Scholar 

  • Maksymowych AB, Simpson LL (1998) Binding and transcytosis of botulinum neurotoxin by polarized human colon carcinoma cells. J Biol Chem 273:21950–21957

    Article  CAS  PubMed  Google Scholar 

  • Maksymowych AB, Simpson LL (2004) Structural features of the botulinum neurotoxin molecule that govern binding and transcytosis across polarized human intestinal epithelial cells. J Pharmacol Exp Ther 310:633–641

    Article  CAS  PubMed  Google Scholar 

  • Mason JT, Xu L, Sheng ZM et al (2006) Liposome polymerase chain reaction assay for the sub-attomolar detection of cholera toxin and botulinum neurotoxin type A. Nat Protoc 1:2003–2011

    Article  CAS  PubMed  Google Scholar 

  • Matsuda M, Sugimoto N, Ozutsumi K et al (1982) Acute botulinum-like intoxication by tetanus neurotoxin in mice. Biochem Biophys Res Commun 104:799–805

    Article  CAS  PubMed  Google Scholar 

  • McLellan K, Das RE, Ekong TA et al (1996) Therapeutic botulinum type A toxin: factors affecting potency. Toxicon 34:975–985

    Article  CAS  PubMed  Google Scholar 

  • Messelhäusser U, Zucker R, Ziegler H et al (2007) Nachweis von Clostridium botulinum Typ A, B, E und F mittels real-time-PCR. J Verbr Lebensm 2:198–201

    Article  Google Scholar 

  • Meyer KF, Gunnison JB (1929) European strains of Cl. botulinum. XXXVI. J Infect Dis 45:96–105

    Article  Google Scholar 

  • Meyer OA, Tilson HA, Byrd WC et al (1979) A method for the routine assessment of fore- and hindlimb grip strength of rats and mice. Neurobehav Toxicol 1:233–236

    CAS  PubMed  Google Scholar 

  • Michalik M, Grzybowski J, LigiÄ™za J et al (1986) Enzyme-linked immunosorbent assay (ELISA) for the detection and differentiation of Clostridium botulinum toxins type A and B. J Immunol Methods 93:225–230

    Article  CAS  PubMed  Google Scholar 

  • Møller V, Scheibel I (1960) Preliminary report on the isolation of an apparently new type of Cl. botulinum. Acta Pathol Microbiol Scand 48:80

    Article  PubMed  Google Scholar 

  • Montecucco C, Schiavo G (1994) Mechanism of action of tetanus and botulinum neurotoxins. Mol Microbiol 13:1–8

    Article  CAS  PubMed  Google Scholar 

  • Moriishi K, Koura M, Abe N et al (1996) Mosaic structures of neurotoxins produced from Clostridium botulinum types C and D organisms. Biochim Biophys Acta 1307:123–126

    Article  PubMed  Google Scholar 

  • Moura H, Terilli RR, Woolfitt AR et al (2011) Studies on botulinum neurotoxins type/C1 and mosaic/DC using endopep-MS and proteomics. FEMS Immunol Med Microbiol 61:288–300

    Article  CAS  PubMed  Google Scholar 

  • Mullis K, Faloona F, Scharf S et al (1986) Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. Cold Spring Harb Symp Quant Biol 51:263–273

    Article  CAS  PubMed  Google Scholar 

  • Notermans S, Dufrenne J, Schothorst M (1978) Enzyme-linked immunosorbent assay for detection of Clostridium botulinum toxin type A. Jpn J Med Sci Biol 31:81–85

    CAS  PubMed  Google Scholar 

  • Notermans S, Dufrenne J, Kozaki S (1979) Enzyme-linked immunosorbent assay for detection of Clostridium botulinum type E toxin. Appl Environ Microbiol 37:1173–1175

    CAS  PubMed  Google Scholar 

  • Notermans S, Dufrenne J, Kozaki S (1982a) The relation between toxicity and toxin-related-antigen contents of Clostridium botulinum types C and D cultures as determined by mouse bioassay and ELISA. Jpn J Med Sci Biol 35:203–211

    CAS  PubMed  Google Scholar 

  • Notermans S, Hagenaars AM, Kozaki S (1982b) The enzyme-linked immunosorbent assay (ELISA) for the detection and determination of Clostridium botulinum toxins A, B, and E. Methods Enzymol 84:223–238

    Article  CAS  PubMed  Google Scholar 

  • O’Brien T, Johnson LH 3rd, Aldrich JL et al (2000) The development of immunoassays to four biological threat agents in a bidiffractive grating biosensor. Biosens Bioelectron 14:815–828

    Article  PubMed  Google Scholar 

  • Ogert RA, Brown JE, Singh BR et al (1992) Detection of Clostridium botulinum toxin A using a fiber optic-based biosensor. Anal Biochem 205:306–312

    Article  CAS  PubMed  Google Scholar 

  • Ohishi I, Sakaguchi G (1980) Oral toxicities of Clostridium botulinum type C and D toxins of different molecular sizes. Infect Immun 28:303–309

    CAS  PubMed  Google Scholar 

  • Ozanich RM Jr, Bruckner-Lea CJ, Warner MG et al (2009) Rapid multiplexed flow cytometric assay for botulinum neurotoxin detection using an automated fluidic microbead-trapping flow cell for enhanced sensitivity. Anal Chem 81:5783–5793

    Article  CAS  PubMed  Google Scholar 

  • Parks BA, Shearer JD, Baudys J et al (2011) Quantification of botulinum neurotoxin serotypes A and B from serum using mass spectrometry. Anal Chem 83:9047–9053

    Article  CAS  PubMed  Google Scholar 

  • Pauly D, Kirchner S, Störmann B et al (2009) Simultaneous quantification of five bacterial and plant toxins from complex matrices using a multiplexed fluorescent magnetic suspension assay. Analyst 134:2028–2039

    Article  CAS  PubMed  Google Scholar 

  • Pearce LB, Borodic GE, First ER et al (1994) Measurement of botulinum toxin activity: evaluation of the lethality assay. Toxicol Appl Pharmacol 128:69–77

    Article  CAS  PubMed  Google Scholar 

  • Peck MW (2009) Biology and genomic analysis of Clostridium botulinum. Adv Microb Physiol 55(183–265):320

    Google Scholar 

  • Pellett S (2012) Progress in cell based assays for botulinum neurotoxin detection. doi: 10.1007/978-3-642-33570-9-12

  • Phillips RW, Abbott D (2008) High-throughput enzyme-linked immunoabsorbant assay (ELISA) electrochemiluminescent detection of botulinum toxins in foods for food safety and defence purposes. Food Addit Contam 25:1084–1088

    Article  CAS  Google Scholar 

  • Piazza TM, Blehert DS, Dunning FM et al (2011) In vitro detection and quantification of botulinum neurotoxin type E activity in avian blood. Appl Environ Microbiol 77:7815–7822

    Article  CAS  PubMed  Google Scholar 

  • Pier CL, Chen C, Tepp WH et al (2011) Botulinum neurotoxin subtype A2 enters neuronal cells faster than subtype A1. FEBS Lett 585:199–206

    Article  CAS  PubMed  Google Scholar 

  • Pires-Alves M, Ho M, Aberle KK et al (2009) Tandem fluorescent proteins as enhanced FRET-based substrates for botulinum neurotoxin activity. Toxicon 53:392–399

    Article  CAS  PubMed  Google Scholar 

  • Poli MA, Rivera VR, Neal D (2002) Development of sensitive colorimetric capture ELISAs for Clostridium botulinum neurotoxin serotypes E and F. Toxicon 40:797–802

    Article  CAS  PubMed  Google Scholar 

  • Popoff MR, Walker JM (2003) Detection of toxigenic Clostridia. Methods Mol Biol 216:137–152

    CAS  PubMed  Google Scholar 

  • Poras H, Ouimet T, Orng SV et al (2009) Detection and quantification of botulinum neurotoxin type a by a novel rapid in vitro fluorimetric assay. Appl Environ Microbiol 75:4382–4390

    Article  CAS  PubMed  Google Scholar 

  • Posthuma-Trumpie GA, Korf J, van Amerongen A (2009) Lateral flow (immuno)assay: its strengths, weaknesses, opportunities and threats. A literature survey. Anal Bioanal Chem 393:569–582

    Article  CAS  PubMed  Google Scholar 

  • Potter MD, Meng JH, Kinsey P (1993) An ELISA for detection of botulinal toxin types A, B, and E in inoculated food samples. J Food Protect 56:856–861

    CAS  Google Scholar 

  • Poulain B, Rossetto O, Deloye F et al (1993) Antibodies against rat brain vesicle-associated membrane protein (synaptobrevin) prevent inhibition of acetylcholine release by tetanus toxin or botulinum neurotoxin type B. J Neurochem 61:1175–1178

    Article  CAS  PubMed  Google Scholar 

  • Poxton IR (1984) Demonstration of the common antigens of Clostridium botulinum, C. sporogenes and C. novyi by an enzyme-linked immunosorbent assay and electroblot transfer. J Gen Microbiol 130:975–981

    CAS  PubMed  Google Scholar 

  • Poxton IR, Byrne MD (1984) Demonstration of shared antigens in the genus Clostridium by an enzyme-linked immunosorbent assay. J Med Microbiol 17:171–176

    Article  CAS  PubMed  Google Scholar 

  • Prévot V, Tweepenninckx F, van Nerom E et al (2007) Optimization of polymerase chain reaction for detection of Clostridium botulinum type C and D in bovine samples. Zoonoses Public Health 54:320–327

    Article  PubMed  Google Scholar 

  • Rajkovic A, El Moualij B, Fikri Y et al (2012) Detection of Clostridium botulinum neurotoxins A and B in milk by ELISA and immuno-PCR at higher sensitivity than mouse bio-assay. Food Anal Methods 5:319–326

    Article  Google Scholar 

  • Raphael BH, Andreadis JD (2007) Real-time PCR detection of the nontoxic nonhemagglutinin gene as a rapid screening method for bacterial isolates harboring the botulinum neurotoxin (A–G) gene complex. J Microbiol Methods 71:343–346

    Article  CAS  PubMed  Google Scholar 

  • Raphael BH, Luquez C, McCroskey LM et al (2008) Genetic homogeneity of Clostridium botulinum type A1 strains with unique toxin gene clusters. Appl Environ Microbiol 74:4390–4397

    Article  CAS  PubMed  Google Scholar 

  • Raphael BH, Choudoir MJ, Luquez C et al (2010a) Sequence diversity of genes encoding botulinum neurotoxin type F. Appl Environ Microbiol 76:4805–4812

    Article  CAS  PubMed  Google Scholar 

  • Raphael BH, Joseph LA, McCroskey LM et al (2010b) Detection and differentiation of Clostridium botulinum type A strains using a focused DNA microarray. Mol Cell Probes 24:146–153

    Article  CAS  PubMed  Google Scholar 

  • Rasetti-Escargueil C, Jones RG, Liu Y et al (2009) Measurement of botulinum types A, B and E neurotoxicity using the phrenic nerve-hemidiaphragm: improved precision with in-bred mice. Toxicon 53:503–511

    Article  CAS  PubMed  Google Scholar 

  • Rasetti-Escargueil C, Liu Y, Rigsby P et al (2011) Phrenic nerve-hemidiaphragm as a highly sensitive replacement assay for determination of functional botulinum toxin antibodies. Toxicon 57:1008–1016

    Article  CAS  PubMed  Google Scholar 

  • Rasooly R, Do PM (2008) Development of an in vitro activity assay as an alternative to the mouse bioassay for Clostridium botulinum neurotoxin type A. Appl Environ Microbiol 74:4309–4313

    Article  CAS  PubMed  Google Scholar 

  • Rasooly R, Do PM (2010) Clostridium botulinum neurotoxin type B Is heat-stable in milk and not inactivated by pasteurization. J Agric Food Chem 58:12557–12561

    Article  CAS  Google Scholar 

  • Rasooly R, Stanker LH, Carter JM et al (2008) Detection of botulinum neurotoxin-A activity in food by peptide cleavage assay. Int J Food Microbiol 126:135–139

    Article  CAS  PubMed  Google Scholar 

  • Ren F, Pearton SJ (2012) Sensors using AlGaN/GaN based high electron mobility transistor for environmental and bio-applications. Phys Status Solidi C 9:393–398

    Article  CAS  Google Scholar 

  • Restani L, Antonucci F, Gianfranceschi L et al (2011) Evidence for anterograde transport and transcytosis of botulinum neurotoxin A (BoNT/A). J Neurosci 31:15650–15659

    Article  CAS  PubMed  Google Scholar 

  • Rivera VR, Gamez FJ, Keener WK et al (2006) Rapid detection of Clostridium botulinum toxins A, B, E, and F in clinical samples, selected food matrices, and buffer using paramagnetic bead-based electrochemiluminescence detection. Anal Biochem 353:248–256

    Article  CAS  PubMed  Google Scholar 

  • Ruge DR, Dunning FM, Piazza TM et al (2011) Detection of six serotypes of botulinum neurotoxin using fluorogenic reporters. Anal Biochem 411:200–209

    Article  CAS  PubMed  Google Scholar 

  • Rummel A (2012) Double Receptor ancharage of botulinum neurotoxins accounts for thier exquisite neurospecificity. doi: 10.1007/978-3-642-3-570-9-4

  • Saiki RK, Gelfand DH, Stoffel S et al (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi G (1982) Clostridium botulinum toxins. Pharmacol Ther 19:165–194

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi G, Sakaguchi S, Kozaki S et al (1974) Cross reaction in reversed passive hemagglutination between Clostridium botulinum type A and B toxins and its avoidance by the sue of anti-toxic component immunoglobulin isolated by affinity chromatography. Jpn J Med Sci Biol 27:161–172

    CAS  PubMed  Google Scholar 

  • Sakamoto T, Torii Y, Takahashi M et al (2009) Quantitative determination of the biological activity of botulinum toxin type A by measuring the compound muscle action potential (CMAP) in rats. Toxicon 54:857–861

    Article  CAS  PubMed  Google Scholar 

  • Sakuma T, Kurosaki Y, Fujinami Y et al (2009) Rapid and simple detection of Clostridium botulinum types A and B by loop-mediated isothermal amplification. J Appl Microbiol 106:1252–1259

    Article  CAS  PubMed  Google Scholar 

  • Sánchez-Hernández L, Cifuentes A, Jiménez B et al (2008) Detection of Clostridium botulinum neurotoxin coding genes: analysis of PCR products by real time versus capillary gel electrophoresis methods. Eur Food Res Technol 227:495–502

    Article  CAS  Google Scholar 

  • Sapsford KE, Taitt CR, Loo N et al (2005) Biosensor detection of botulinum toxoid A and staphylococcal enterotoxin B in food. Appl Environ Microbiol 71:5590–5592

    Article  CAS  PubMed  Google Scholar 

  • Sapsford KE, Sun S, Francis J et al (2008) A fluorescence detection platform using spatial electroluminescent excitation for measuring botulinum neurotoxin A activity. Biosens Bioelectron 24:618–625

    Article  CAS  PubMed  Google Scholar 

  • Satterfield BA, Stewart AF, Lew CS et al (2010) A quadruplex real-time PCR assay for rapid detection and differentiation of the Clostridium botulinum toxin genes A, B, E and F. J Med Microbiol 59:55–64

    Article  CAS  PubMed  Google Scholar 

  • Schiavo G, Rossetto O, Catsicas S et al (1993) Identification of the nerve terminal targets of botulinum serotypes A, D, and E. J Biol Chem 268:23784–23786

    CAS  PubMed  Google Scholar 

  • Schmidt JJ, Stafford RG, Millard CB (2001) High-throughput assays for botulinum neurotoxin proteolytic activity: serotypes A, B, D, and F. Anal Biochem 296:130–137

    Article  CAS  PubMed  Google Scholar 

  • Scotcher MC, Cheng LW, Stanker LH (2010) Detection of botulinum neurotoxin serotype B at sub mouse LD50 levels by a sandwich immunoassay and its application to toxin detection in milk. PLoS ONE 5:e11047

    Article  PubMed  CAS  Google Scholar 

  • Seddon HR (1922) Bulbar paralysis in cattle due to the action of toxicogenic bacillus, with a discussion on the relationship of the condition to forage poisoning (botulism). J Comp Pathol Therapeut 35:147–190

    Google Scholar 

  • Sesardic D, McLellan K, Ekong TA et al (1996) Refinement and validation of an alternative bioassay for potency testing of therapeutic botulinum type A toxin. Pharmacol Toxicol 78:283–288

    Article  CAS  PubMed  Google Scholar 

  • Sesardic D, Leung T, Gaines Das R (2003) Role for standards in assays of botulinum toxins: international collaborative study of three preparations of botulinum type A toxin. Biologicals 31:265–276

    Article  CAS  PubMed  Google Scholar 

  • Sesardic D, Jones RG, Leung T et al (2004) Detection of antibodies against botulinum toxins. Mov Disord 19:S85–S91

    Article  PubMed  Google Scholar 

  • Sharma SK, Eblen BS, Bull RL et al (2005) Evaluation of lateral-flow Clostridium botulinum neurotoxin detection kits for food analysis. Appl Environ Microbiol 71:3935–3941

    Article  CAS  PubMed  Google Scholar 

  • Sharma SK, Ferreira JL, Eblen BS et al (2006) Detection of type A, B, E, and F Clostridium botulinum neurotoxins in foods by using an amplified enzyme-linked immunosorbent assay with digoxigenin-labeled antibodies. Appl Environ Microbiol 72:1231–1238

    Article  CAS  PubMed  Google Scholar 

  • Shin NR, Yoon SY, Shin JH et al (2007) Development of enrichment semi-nested PCR for Clostridium botulinum types A, B, E, and F and its application to Korean environmental samples. Mol Cells 24:329–337

    CAS  PubMed  Google Scholar 

  • Shine N, Eaton L, Crawford K (2002) A continuous fluorimetric assay for high throughput screening for BoNT/A inhibitors. Naunyns Schmiedebergs Arch Pharmacol 365(Suppl. 2), Abstract R128

    Google Scholar 

  • Shone C, Wilton-Smith P, Appleton N et al (1985) Monoclonal antibody-based immunoassay for type A Clostridium botulinum toxin is comparable to the mouse bioassay. Appl Environ Microbiol 50:63–67

    CAS  PubMed  Google Scholar 

  • Shriver-Lake LC, Ogert RA, Ligler FS (1993) A fiber-optic evanescent-wave immunosensor for large molecules. Sens Actuators B Chem 11:239–243

    Article  Google Scholar 

  • Simpson LL (1973) The interaction between divalent cations and botulinum toxin type A in the paralysis of the rat phrenic nerve-hemidiaphragm preparation. Neuropharmacology 12:165–176

    Article  CAS  PubMed  Google Scholar 

  • Simpson LL (1974) Studies on the binding of botulinum toxin type A to the rat phrenic nerve-hemidiaphragm preparation. Neuropharmacology 13:683–691

    Article  CAS  PubMed  Google Scholar 

  • Simpson LL (2004) Identification of the major steps in botulinum toxin action. Annu Rev Pharmacol Toxicol 44:167–193

    Article  CAS  PubMed  Google Scholar 

  • Simpson LL, Tapp JT (1967) Actions of calcium and magnesium on the rate of onset of botulinum toxin paralysis of the rat diaphragm. Int J Neuropharmacol 6:485–492

    Article  CAS  PubMed  Google Scholar 

  • Smith TJ, Lou J, Geren IN et al (2005) Sequence variation within botulinum neurotoxin serotypes impacts antibody binding and neutralization. Infect Immun 73:5450–5457

    Article  CAS  PubMed  Google Scholar 

  • Stanker LH, Merrill P, Scotcher MC et al (2008) Development and partial characterization of high-affinity monoclonal antibodies for botulinum toxin type A and their use in analysis of milk by sandwich ELISA. J Immunol Methods 336:1–8

    Article  CAS  PubMed  Google Scholar 

  • Strotmeier J, Willjes G, Binz T et al (2012) Human synaptotagmin-II is not a high affinity receptor for botulinum neurotoxin B and G: increased therapeutic dosage and immunogenicity. FEBS Lett 586:310–313

    Article  CAS  PubMed  Google Scholar 

  • Sugiyama H (1980) Clostridium botulinum neurotoxin. Microbiol Rev 44:419–448

    CAS  PubMed  Google Scholar 

  • Sugiyama H, Oishi I, Dasgupta BR (1974) Evaluation of type A botulinal toxin assays that use antitoxin to crystalline toxin. Appl Microbiol 27:333–336

    CAS  PubMed  Google Scholar 

  • Sugiyama H, Brenner SL, Dasgupta BR (1975) Detection of Clostridium botulinum toxin by local paralysis elicited with intramuscular challenge. Appl Microbiol 30:420–423

    CAS  PubMed  Google Scholar 

  • Sun S, Ossandon M, Kostov Y et al (2009) Lab-on-a-chip for botulinum neurotoxin a (BoNT-A) activity analysis. Lab Chip 9:3275–3281

    Article  CAS  PubMed  Google Scholar 

  • Sun S, Francis J, Sapsford KE et al (2010) Multi-wavelength Spatial LED illumination based detector for in vitro detection of botulinum neurotoxin A activity. Sens Actuators B Chem 146:297–306

    Article  PubMed  CAS  Google Scholar 

  • Szabo EA, Pemberton JM, Desmarchelier PM (1992) Specific detection of Clostridium botulinum type B by using the polymerase chain reaction. Appl Environ Microbiol 58:418–420

    CAS  PubMed  Google Scholar 

  • Szabo EA, Pemberton JM, Desmarchelier PM (1993) Detection of the genes encoding botulinum neurotoxin types A to E by the polymerase chain reaction. Appl Environ Microbiol 59:3011–3020

    CAS  PubMed  Google Scholar 

  • Szabo EA, Pemberton JM, Gibson AM et al (1994) Polymerase chain reaction for detection of Clostridium botulinum types A, B and E in food, soil and infant faeces. J Appl Bacteriol 76:539–545

    Article  CAS  PubMed  Google Scholar 

  • Szílagyi M, Rivera VR, Neal D et al (2000) Development of sensitive colorimetric capture ELISAs for Clostridium botulinum neurotoxin serotypes A and B. Toxicon 38:381–389

    Google Scholar 

  • Takahashi M, Kameyama S, Sakaguchi G (1990) Assay in mice for low levels of Clostridium botulinum toxin. Int J Food Microbiol 11:271–277

    Article  CAS  PubMed  Google Scholar 

  • Takahashi H, Takakura C, Kimura B (2010) A quantitative real-time PCR method for monitoring Clostridium botulinum type A in rice samples. J Food Prot 73:688–694

    CAS  PubMed  Google Scholar 

  • Takeda M, Tsukamoto K, Kohda T et al (2005) Characterization of the neurotoxin produced by isolates associated with avian botulism. Avian Dis 49:376–381

    Article  PubMed  Google Scholar 

  • Takeshi K, Fujinaga Y, Inoue K et al (1996) Simple method for detection of Clostridium botulinum type A to F neurotoxin genes by ploymerase chain reaction. Microbiol Immunol 40:5–11

    CAS  PubMed  Google Scholar 

  • Terilli RR, Moura H, Woolfitt AR et al (2011) A historical and proteomic analysis of botulinum neurotoxin type/G. BMC Microbiol 11:232

    Article  CAS  PubMed  Google Scholar 

  • Theiler A, Robinson EM (1927) Der Botulismus der Haustiere. Z Infektionskr Haustiere 31:165–220

    Google Scholar 

  • Thomas RJ (1991) Detection of Clostridium botulinum types C and D toxin by ELISA. Aust Vet J 68:111–113

    Article  CAS  PubMed  Google Scholar 

  • Torii Y, Goto Y, Takahashi M et al (2010a) Quantitative determination of biological activity of botulinum toxins utilizing compound muscle action potentials (CMAP), and comparison of neuromuscular transmission blockage and muscle flaccidity among toxins. Toxicon 55:407–414

    Article  CAS  PubMed  Google Scholar 

  • Torii Y, Takahashi M, Ishida S et al (2010b) Quantification of potency of neutralizing antibodies to botulinum toxin using compound muscle action potential (CMAP). Toxicon 55:662–665

    Article  CAS  PubMed  Google Scholar 

  • Torii Y, Kiyota N, Sugimoto N et al (2011) Comparison of effects of botulinum toxin subtype A1 and A2 using twitch tension assay and rat grip strength test. Toxicon 57:93–99

    Article  CAS  PubMed  Google Scholar 

  • Umeda K, Seto Y, Kohda T et al (2009) Genetic characterization of Clostridium botulinum associated with type B infant botulism in Japan. J Clin Microbiol 47:2720–2728

    Article  CAS  PubMed  Google Scholar 

  • Umeda K, Seto Y, Kohda T et al (2010) A novel multiplex PCR method for Clostridium botulinum neurotoxin type A gene cluster typing. Microbiol Immunol 54:308–312

    CAS  PubMed  Google Scholar 

  • van Baar BL, Hulst AG, de Jong AL et al (2002) Characterisation of botulinum toxins type A and B, by matrix-assisted laser desorption ionisation and electrospray mass spectrometry. J Chromatogr A 970:95–115

    Article  PubMed  Google Scholar 

  • van Baar BL, Hulst AG, de Jong AL et al (2004) Characterisation of botulinum toxins type C, D, E, and F by matrix-assisted laser desorption ionisation and electrospray mass spectrometry. J Chromatogr A 1035:97–114

    Article  PubMed  CAS  Google Scholar 

  • van Ermengem E (1897) Ueber einen neuen anaëroben Bacillus und seine Beziehungen zum Botulismus. Z Hyg 26:1–56

    Google Scholar 

  • Varnum SM, Warner MG, Dockendorff B et al (2006) Enzyme-amplified protein microarray and a fluidic renewable surface fluorescence immunoassay for botulinum neurotoxin detection using high-affinity recombinant antibodies. Anal Chim Acta 570:137–143

    Article  CAS  PubMed  Google Scholar 

  • Viscidi R, Laughon BE, Hanvanich M et al (1984) Improved enzyme immunoassays for the detection of antigens in fecal specimens. Investigation and correction of interfering factors. J Immunol Methods 67:129–143

    Article  CAS  PubMed  Google Scholar 

  • Volland H, Lamourette P, Nevers M-C et al (2008) A sensitive sandwich enzyme immunoassay for free or complexed Clostridium botulinum neurotoxin type A. J Immunol Methods 330:120–129

    Article  CAS  PubMed  Google Scholar 

  • Wang D, Baudys J, Kalb SR et al (2011) Improved detection of botulinum neurotoxin type A in stool by mass spectrometry. Anal Biochem 412:67–73

    Article  CAS  PubMed  Google Scholar 

  • Warner MG, Grate JW, Tyler A et al (2009) Quantum dot immunoassays in renewable surface column and 96-well plate formats for the fluorescence detection of botulinum neurotoxin using high-affinity antibodies. Biosens Bioelectron 25:179–184

    Article  CAS  PubMed  Google Scholar 

  • Weingart OG, Schreiber T, Mascher C et al (2010) The case of botulinum toxin in milk: experimental data. Appl Environ Microbiol 76:3293–3300

    Article  CAS  PubMed  Google Scholar 

  • Weingart OG, Gao H, Crevoisier F et al (2012) A bioanalytical platform for simultaneous detection and quantification of biological toxins. Sensors (Basel) 12:2324–2339

    Article  CAS  Google Scholar 

  • Wictome M, Newton K, Jameson K et al (1999a) Development of an in vitro bioassay for Clostridium botulinum type B neurotoxin in foods that is more sensitive than the mouse bioassay. Appl Environ Microbiol 65:3787–3792

    CAS  PubMed  Google Scholar 

  • Wictome M, Newton KA, Jameson K et al (1999b) Development of in vitro assays for the detection of botulinum toxins in foods. FEMS Immunol Med Microbiol 24:319–323

    Article  CAS  PubMed  Google Scholar 

  • Wilder-Kofie TD, Lúquez C, Adler M et al (2011) An alternative in vivo method to refine the mouse bioassay for botulinum toxin detection. Comp Med 61:235–242

    CAS  PubMed  Google Scholar 

  • Woudstra C, Skarin H, Anniballi F et al (2012) Neurotoxin gene profiling of Clostridium botulinum types C and D native to different countries within Europe. Appl Environ Microbiol 78:3120–3127

    Article  CAS  PubMed  Google Scholar 

  • Wu HC, Huang YL, Lai SC et al (2001) Detection of Clostridium botulinum neurotoxin type A using immuno-PCR. Lett Appl Microbiol 32:321–325

    Article  CAS  PubMed  Google Scholar 

  • Yamashiro S, Sano Y, Komano A et al (2007) Detection of proteinous toxins using the bio-threat alert system, part 4. Differences in detectability according to manufactural lots and according to toxin subtypes. Forensic Toxicol 25:80–83

    Article  CAS  Google Scholar 

  • Yoon SY, Chung GT, Kang DH et al (2005) Application of real-time PCR for quantitative detection of Clostridium botulinum type A toxin gene in food. Microbiol Immunol 49:505–511

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Diana Pauly and Ursula Erikli for critically reading the manuscript. This work was supported by grants from the Federal Ministry of Education and Research (BiGRUDI project, 13N9601; zoonosis project, 01KI1021).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Brigitte G. Dorner .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Dorner, M.B., Schulz, K.M., Kull, S., Dorner, B.G. (2012). Complexity of Botulinum Neurotoxins: Challenges for Detection Technology. 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_11

Download citation

Publish with us

Policies and ethics