Botulinum Neurotoxin Archives

List Labs scours the internet monthly, looking for citations referencing our products. We are highly intrigued by, and love to investigate the different ways researchers use our products. Scientists world-wide have used our toxins for research and have produced interesting results.

List Labs History of working with Botulinum Neurotoxin

List Labs has developed sensitive assays used by pharmaceutical companies, research universities and government agencies to detect Botulinum Toxin Type A in complex samples and to screen for potential inhibitors. List Labs also has a bifunctional assay for Botulinum Type A which measures SV2c receptor binding enzymatic activity.

List Labs is a well-known quality provider of bacterial toxins for research. We harness our vast experience, expertise, state of the art equipment and facilities to bring researchers some of the purest products available.

You can purchase List Labs Botulinum Neurotoxin research reagents here, and view our full catalog of products here.

View our Botulinum neurotoxin citations infographic below:

By: T.J. Smith

The answer as to whether the botulinum neurotoxin (BoNT)-producing bacteria comprised six separate species required a complete revolution in microbial classification. Up to the turn of the last century, bacterial differentiations were based on morphological characteristic and biochemical activities, known collectively as phenotypic characteristics. However, the discovery of DNA as the ultimate code of life led to technological methodologies enabling the sequencing and comparisons of individual genes and, ultimately, entire bacterial genomes. Initial studies used DNA-DNA hybridization (DDH) techniques which, due to the cumbersome nature of the assays, was followed quickly by comparative analyses of 16s rRNA gene, which is a highly conserved gene that is present among all bacterial species (Rossello-Mora and Amann 2001). The results of these studies were remarkably similar, providing confidence in the predictability of both assays for bacterial speciation.

Setting the Stage for Current Classifications

16s rRNA analyses of various clostridial species verified earlier thoughts about their relationships (Collins 1998). The proteolytic BoNT type A, B, and F-producing C. botulinum bacteria were found to cluster with closely related C. sporogenes, while nonproteolytic BoNT type B, E, and F-producing C. botulinum were determined to be a distinct species cluster. Type C and D-producing bacteria were closely related to non-neurotoxigenic C. novyi strains. Type G-producing bacteria, along with nontoxic C. subterminale, were deemed a distinct species, designated C. argentinense. Type F-producing C. baratii and type E-producing C. butryricum were both found to be indistinguishable from their nontoxic counterparts using these techniques. Thus, in addition to the neurotoxin-producing bacteria that had reverted to nontoxicity, additional connections between toxic and nontoxic organisms were seen. This completely contradicted the theory that any botulinum neurotoxin-producing bacteria should be named “C. botulinum” and set the stage for current classifications based on whole genome analysis for differentiation of bacterial strains.

Seven Distinct Clostridial Species Produce Botulinum Neurotoxins

Currently, this analysis can be done at a very fine level, as each of the approximately 4 million nucleotide residues that reside within an average clostridial genome can be identified and compared. Individual nucleotide differences among core, or shared, genes within a genome are analyzed using numerical computations that help determine species/species interfaces (Richter and Rossello-Mora 2009). This technique is known as average nucleotide identity, or ANI. It is known that the same bacterial isolate can mutate over time in the laboratory, so that sequencing of the same isolate over time should show a few minimal differences. However, larger scale differences are seen in different strains within the same species and further numbers of differences separate distinct species. These relationships are strengthened through analysis of large numbers of genomes, and this has helped to support an avalanche of bacterial genome sequencing studies. To date over 200 Clostridium botulinum strains plus over 60 closely related strains have been sequenced and subjected to comparative analysis (https://www.ncbi.nlm.nih.gov/pubmed). The results confirm that seven distinct clostridial species are capable of producing botulinum neurotoxins (Williamson, Sahl et al 2016). These include three groups and four species. The first, Group I, proteolytic C. botulinum, had a name change, to C. parabotulinum and then changed back to C. botulinum Group I (Smith, Williamson et al 2018); Group II includes the nonproteolytic C. botulinum type B, E, and F toxin producers, and Group III, type C and D toxin-producing C. botulinum, a group name which has had a suggested change to C. novyi sensu lato (Skarin, Hafstrom et al 2011). In addition to these groups, four genetically distinct species which may produce botulinum toxin are C. argentinense; C. baratii; C. butyricum; and C. sporogenes.

Different species may produce the same toxin and different toxins may be produced by the same bacterial species. In addition, there are documented non-neurotoxigenic members represented in each species. A listing of BoNT-producing bacteria and their characteristics is shown in Table 1 (Hatheway 1988, Collins 1998).

Table 1. An abbreviated table showing some major characteristics of various clostridia, that produce botulinum toxin.

Species/group	Toxins produced	Lipase	Lecithinase	Proteolytic
C. botulinum Group I	A, B, F, Ab, Ba, Af, HA	+	–	yes
C. botulinum Group II	B, E, F	+	–	no
C. botulinum Group III	C, D	+	variable	variable
C. argentinense	G	–	–	yes
C.baratii	F	–	+	no
C. butyricum	E	–	–	no
C. sporogenes	B	+	–	yes

It has been determined that there is a great deal of diversity among the bacteria that produce botulinum toxins, as well as among the toxins themselves. The seven toxin serotypes differ to such a large extent that the antisera to one type cannot neutralize the toxin of a different type. However, genetic analysis of these toxins has revealed yet another level of diversity. The identification and study of BoNT subtypes has been the subject of increasing interest in the past three decades, leading to a whole new understanding of the complexity of these proteins.

About List Labs

List Labs offers over 100 reagents including Botulinum Toxins. These products are used in a wide variety of scientific research studies. You can read about some of them on our citation page. Contact us today to discuss your next project.

About the Author

Theresa Smith has studied botulinum neurotoxins for over 25 years, specializing in toxin countermeasure research, and is considered a leading expert regarding diversity in botulinum neurotoxins as well as the organisms that produce these toxins.

References

Collins, M. D. (1998). “Phylogeny and taxonomy of the food-borne pathogen Clostridium botulinum and its neurotoxins.” J Appl Microbiol 84: 5-17. PMID: 15244052

Hatheway, C. L. (1988). Botulism. In A. Balows, W. H. Hausler, J. Ohashi and A. Turano (ed) Laboratory Diagnosis of Infectious Diseases New York, Springer-Verlag: 111-133.

Richter, M. and R. Rossello-Mora (2009). “Shifting the genomic gold standard for the prokaryotic species definition.” Proc Natl Acad Sci U S A 106(45): 19126-19131. PMID: 19855009

Rossello-Mora, R. and R. Amann (2001). “The species concept for prokaryotes.” FEMS Microbiol Rev 25(1): 39-67. PMID: 11152940

Skarin, H., T. Hafstrom, J. Westerberg and B. Segerman (2011). “Clostridium botulinum group III: a group with dual identity shaped by plasmids, phages and mobile elements.” BMC Genomics 12(185): 1-13. PMID: 21486474

Smith, T. J., C. H. Williamson, K. Hill, J. W. Sahl and P. Keim (2018). “Botulinum neurotoxin-producing bacteria – isn’t it time we called a species a species?” MBio in press.

Williamson, C. H., J. W. Sahl, T. J. Smith, G. Xie, B. T. Foley, L. A. Smith, R. A. Fernandez, M. Lindstrom, H. Korkeala, P. Keim, J. Foster and K. Hill (2016). “Comparative genomic analyses reveal broad diversity in botulinum-toxin-producing Clostridia.” BMC Genomics 17: 180. PMID: 26939550

By: T.J. Smith

Gram strain of C. botulinum

Origins of Botulinum Toxin Types – relationships between toxins and the bacteria that produce them

Soon after the discovery that botulism was caused by a toxin, multiple toxin types were identified. Initial characterizations were based mainly on serological differences, however other anomalies were noted, such as differences in toxicity, sensitivity or resistance of different animal species to intoxication, cultural or morphological characteristics, and, finally, genetic differences.

Historical Differentiation of Bacterial Organisms

In the late 1800s and early 1900s, differentiation of bacterial organisms was mostly a matter of observations related to colony and cell characteristics, growth characteristics, and biochemical usage. Organisms were often partly identified according to their Gram stain characteristics, either Gram stain positive (purple) or Gram negative (red), often with cocci (balls) or rod (rectangular) shapes. Variations in shape, size, or coloration served to further delineate certain genera, such as with the paired kidney bean shapes of Neisseria or the comma-shaped Vibrios. The presence of Gram positive organisms with subterminal oval spores served to further identify the anaerobic bacteria as Clostridium.

Additional delineations have come from biochemical reactions of the bacteria. These may involve the ability to break down and utilize different proteins in the environment (proteolysis) or to utilize various carbohydrates through sugar fermentation. Examples of these assessments include liquification of gelatin or color changes triggered by a lowered pH due to fermentation of lactose or sucrose. With toxin-producing clostridial species, the ability to break down fats using lipases (positive lipase reaction) coupled with an inability to break down lecithin (negative lecithinase reaction) were hallmarks of the presence of Clostridium botulinum. Differences in optimal growth temperatures and resistance of spores to heat treatment have also been used as tools for differentiation.

Different Bacterial Variants Found to Produce Both Same and Different Toxins

Differences in these characteristics were noted from the beginning, when the Ellezelles strain characterized by Dr. E. Van Ermengem was found to be a nonproteolytic organism that favored a moderate optimal growth temperature of 25-30° C, while the Darmstadt strain identified by Dr. G. Landmann was definitely proteolytic with a higher optimal growth temperature of approximately 37° C (Van Ermengem 1897, Leuchs 1910). The Darmstadt strain produced type A toxin, while the Ellezelles strain produced type B toxin. The fact that the two strains produced different toxin serotypes initially linked these toxin differences with the bacterial differences. However, it was quickly discovered that different bacterial variants could produce the same toxin and the same bacteria could produce different toxins. C. botulinum strains that produced type A toxin were identified from the west coast of the United States, while virtually identical strains from the east coast were identified as type B (Burke 1919). However, the bacteria producing type B toxins in Europe differed from those in the U.S. in that the European strains were nonproteolytic, while the U.S. strains were uniformly proteolytic. This provided clear evidence that the bacterial types and the toxins they produced were not linked.

In 1922, the literature began to reflect these bacterial differences by identifying proteolytic organisms that produce botulinum neurotoxin as “Clostridium parabotulinum” and nonproteolytic organisms remained “Clostridium botulinum”. Dr. H. R. Seddon first used the term C. parabotulinum to distinguish his type C strains, isolated from cattle in Australia, from those of Dr. Ida Bengtson, isolated from fly larvae in the U.S. (Bengtson 1922, Seddon 1922). In addition to difficulties encountered when neutralizing her toxins with his antisera, the strains themselves appeared to differ in proteolytic tendencies. For the next 30 years proteolytic type A and B strains and Seddon type C strains were labeled C. parabotulinum while the nonproteolytic European type B strains and U.S. type C strains were designated C. botulinum.

When type E-producing bacteria were characterized, they were found to be uniformly closely related to the nonproteolytic type B strains (Hazen 1937), and on rare occasions both proteolytic and nonproteolytic bacterial strains that produced type F toxin were isolated (Moller and Scheibel 1960, Eklund, Poysky et al. 1967).

Bacterial Variants of Botulinum Toxins

Despite these obvious bacterial strain differences, it was proposed in 1953 and decided over the following decade to designate all botulinum neurotoxin-producing organisms as “Clostridium botulinum” on the basis of that single overriding characteristic. This was problematic as bacterial strains were already known that had produced botulinum toxin in the past but were no longer toxin producers. A major surprise came with the identification of an entirely different clostridial species, C. baratii, that produced type F toxin (Hall, McCroskey et al. 1985). Shortly after this came the identification of a C. butyricum strain that produced type E toxin (Aureli, Fenicia et al. 1986). In addition, the characterization of the bacteria that produced type G toxin revealed that it was a distinct species, prompting its designation as C. argentinense (Gimenez and Ciccarelli 1970).

Based on phenotypic characteristics, at least six different bacterial variants that could produce one (or more) botulinum neurotoxins have been identified. The question of whether these variants are a single entity or represent separate species was later answered using technological advances in genetic analyses.

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References

Aureli, P., L. Fenicia, B. Pasolini, M. Gianfranceschi, L. M. McCroskey and C. L. Hatheway (1986). “Two cases of type E infant botulism caused by neurotoxigenic Clostridium butyricum in Italy.” J Infect Dis 154(2): 207-211.

Bengtson, I. (1922). “Preliminary note on a toxin-producing anaerobe isolated from the larvae of Lucilia caesar.” Pub Health Repts 37: 164-170.

Burke, G. S. (1919). “Notes on Bacillus botulinus.” J Bact 4: 555-571.

Eklund, M. W., F. T. Poysky and D. I. Wieler (1967). “Characteristics of Clostridium botulinum type F isolated from the Pacific Coast of the United States.” Appl Microbiol 15(6): 1316-1323.

Gimenez, D. F. and A. S. Ciccarelli (1970). “Another type of Clostridium botulinum.” Zentralbl Bakteriol Parasitenk Infektionskr Hyg Abt 215: 221-224.

Hall, J. D., L. M. McCroskey, B. J. Pincomb and C. L. Hatheway (1985). “Isolation of an organism resembling Clostridium barati which produces type F botulinal toxin from an infant with botulism.” J Clin Microbiol 21(4): 654-655.

Hazen, E. L. (1937). “A strain of B. botulinus not classified as type A, B, or C.” J Infect Dis 60: 260-264.

Leuchs, J. (1910). “Beitraege zur kenntnis des toxins und antitoxins des Bacillus botulinus.” Z Hyg Infekt 76: 55-84.

Moller, V. and I. Scheibel (1960). “Preliminary report of an apparently new type of Cl. botulinum ” Acta Path Microbiol Scand 48: 80.

Seddon, H. R. (1922). “Bulbar paralysis in cattle due to the action of a toxicogenic bacillus, with a discussion on the relationship of the condition to forage poisoning (botulism).” J Comp Path Ther 35: 147-190.

Van Ermengem, E. (1897). “A new anaerobic bacillus and its relation to botulism (originally published as “Ueber einen neuen anaeroben Bacillus und seine beziehungen zum botulismus” in Zeitschrift fur Hygiene und Infektionskrankheiten, 26:1-56) ” Clin Infect Dis 4: 701-719.

3D Rendering of Botulinum Toxin Protein

By: T.J. Smith

Following a botulism outbreak due to contaminated ham that severely sickened 10 and resulted in the death of three people in Ellezelles, Belgium, a review and case study on botulism was published by a researcher named Emile Van Ermengem (Van Ermengem 1897). While Van Ermengem was not the first to study this syndrome, his article supplied critical information defining botulism as a type of food poisoning having specific paralytic symptoms. He determined that the illness was an intoxication, not an infection, and that its cause was a bacterial toxin. He was also able to isolate and characterize the organism responsible for the toxin as an anaerobic spore-forming bacillus, which he named Bacillus botulinus (later renamed Clostridium botulinum). “Botulinus” is the latin word for sausages, and this nomenclature was used due to the historic link between botulism and improperly processed sausages, particularly blood sausages. His careful and painstaking research provided the foundation for future studies on botulism, its causes and treatments.

During this time, botulism was thought to be related specifically to improperly processed meat, such as sausages and ham, and caused by a single monospecific toxin. Within the next decade both of these theories were proven wrong. In 1904, Dr. G. Landmann isolated a botulinum toxin-producing bacterial strain from preserved bean salad which had caused 11 deaths in Darmstadt, Germany (Landmann 1904). This was the first reporting of botulism due to a source other than meat or fish. In 1910, Leuchs showed that the Ellezelles strain from Van Ermengem and the Darmstadt strain from Landmann were immunologically distinct toxins, providing the first evidence that all botulinum neurotoxins were not the same (Leuchs 1910). This marked the beginning of a century of study related to botulinum neurotoxin diversity which included clinical case reviews and morphological, immunological, and, most recently, genetic studies.

As the bacteria responsible for botulinum neurotoxins initially seemed to be nearly identical in morphology and cultural characteristics, early delineations were the result of serological studies, which were apparently the “hot new thing” of the day. Antisera produced using a particular bacterial strain was tested against other strains to determine relationships among both the toxins and the bacteria that produced them. The assays were both qualitative and quantitative and included agglutination, immuno-absorption, and neutralization techniques (Schoenholz and Meyer 1925). They were originally targeted to both the toxins and the bacteria that produced them, but the emphasis quickly shifted to neutralization of toxins using specific antisera. These antisera, which were predominantly of equine origin, were developed for treatment purposes as well, and they continue to be the only approved treatment for botulism to this day. In 1919, Georgina Burke produced antisera from three strains isolated in California, Oregon, and New York, and she was able to show that the toxins from the two West Coast strains were immunologically identical, while the New York toxin was distinct (Burke 1919). She identified these toxins as type A (West) and Type B (East). Later studies of U. S. strains by K. F. Meyer and B. Dubovsky substantiated her findings (Meyer and Dubovsky 1922).

In the following decades several additional serotypes were identified. In 1922, Dr. Ida Bengtson reported a toxin from a C. botulinum strain that was not neutralized by either type A or type B antisera, which she designated type C (Bengtson 1922). The bacterial strain was isolated from fly larvae that proved to be causative agents in the intoxication of chickens that had ingested these larvae. This illustrates that botulism is not restricted to humans but rather can be seen in a wide variety of animals as well. In fact, differential sensitivities of the toxins in animals has formed a background for discerning various toxin types. In addition, catastrophic losses due to botulism have been noted in domestic fowl, cattle, horses, and even minks and foxes, prompting the development and use of vaccines in these animals for protection. H. R. Seddon isolated a culture that apparently produced type C toxin from an outbreak in cattle in Australia (Seddon 1922). The toxin could be neutralized by Bengtson’s antisera, however, the reverse was not true. This “one-way” neutralization was the first of several anomalies that were discovered when serotyping botulinum neurotoxins.

In 1929, Meyer and Gunnison showed that the toxin from a culture isolated by Theiler and associates in South Africa was immunologically distinct from types A, B, or C. This toxin, which was also related to intoxication in cattle, was designated type D (Meyer and Gunnison 1929).

In the following decade, several botulism cases were noted that were related to ingestion of fish. While Russian scientists were the first to note these unusual cases of botulism, it was Dr. Janet Gunnison who determined the toxins were a new type, and Dr. Elizabeth Hazen who published initial reports on type E botulism cases (Gunnison, Cummings et al. 1936, Hazen 1937). Outbreaks due to dried, smoked, or fermented fish, fish eggs, whale blubber, and seal or walrus meat are common, but there have been rare type E cases related to other foods as well.

The first case due to type F was linked to an outbreak involving duck paste on Langeland Island, Denmark, in 1958 (Moller and Scheibel 1960). Reported cases due to type F are rare and have been restricted to humans so far. Type G was isolated from a cornfield in Argentina in 1969 as part of a soil sampling study conducted by Dr D. F. Gimenez and Dr. A. S. Ciccarelli (Gimenez and Ciccarelli 1970). This type is unusual in that there are no direct reports of intoxications due to type G in people or animals. However, a study of autopsy materials related to sudden deaths due to unknown causes in Switzerland identified type G producing organisms among the samples (Sonnabend, Sonnabend et al. 1981). Why type G is only found in Argentina or Switzerland is a mystery.

As of 1970, there were seven known immunologically distinct botulinum toxin types. However, as we will discover, this was just the beginning of our understanding of the diversity that is seen within botulinum neurotoxins.

About List Labs

About the Author

References

Bengtson, I. (1922). “Preliminary note on a toxin-producing anaerobe isolated from the larvae of Lucilia caesar.” Pub Health Repts 37: 164-170.

Burke, G. S. (1919). “Notes on Bacillus botulinus.” J Bact 4: 555-571.

Gimenez, D. F. and A. S. Ciccarelli (1970). “Another type of Clostridium botulinum.” Zentralbl Bakteriol Parasitenk Infektionskr Hyg Abt 215: 221-224.

Gunnison, J. B., et al. (1936). “Clostridium botulinum type E.” Proc Soc Exp Biol Med 35: 278-280.

Hazen, E. L. (1937). “A strain of B. botulinus not classified as type A, B, or C.” J Infect Dis 60: 260-264.

Landmann, G. (1904). “Uber die ursache der Darmstadter bohnenvergiftung.” Hyg Rundschau 10: 449-452.

Leuchs, J. (1910). “Beitraege zur kenntnis des toxins und antitoxins des Bacillus botulinus.” Z Hyg Infekt 76: 55-84.

Meyer, K. F. and B. Dubovsky (1922). “The distribution of the spores of B. botulinus in the United States. IV.” J Infect Dis 31: 559-594.

Meyer, K. F. and J. B. Gunnison (1929). “South African cultures of Clostridium botulinum and parabotulinum. XXXVII with a description of Cl. botulinum type D, N. SP.” J Infect Dis 45: 106-118.

Moller, V. and I. Scheibel (1960). “Preliminary report of an apparently new type of Cl. botulinum ” Acta Path Microbiol Scand 48: 80.

Schoenholz, P. and K. F. Meyer (1925). “The serologic classification of B. botulinus.” J Immunol 10: 1-53.

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.” J Infect Dis 143: 22-27.

By: Mary N. Wessling, Ph.D. ELS

List Biological Laboratories’ (List Labs) catalog of products is related to furthering research in human health and preventing disease, most commonly as the starting materials for vaccine research & development or production around the world. Vaccines are mainly identified for their capacity to prevent diseases that the body’s innate defensive mechanisms (the skin and specialized cells in the blood, for example) can’t resist unaided. However, there are many other uses for these purified materials in medical research, and you will likely encounter wording on our website that is not part of everyday vocabulary for non-scientists. This article is intended to provide a basic understanding of some of the more frequently used terms and aid you in selecting the products most essential to your projects.

Toxin vs. Toxoid

For starters, what is the difference between “toxin” and “toxoid”. Broadly defined, anything that can cause harm to an organism is a toxin. However, for List Labs’ products and in biological usage, a toxin refers to a bacterial or viral product that has harmful effects when it enters the body (List Labs’ toxins are in a highly purified form). A toxoid is a chemically altered toxin that has reduced or no toxicity and is used for its remaining antigenic activity, which can stimulate an immune response.

Take, for example, cholera, a disease produced by Vibrio cholerae bacteria, possibly through contact with body fluids from a person ill with cholera or through contaminated water supply. Cholera causes severe diarrhea, and untreated, it can be fatal. However, the purified List Labs’ cholera toxin by chemical modification becomes a toxoid that lacks toxic activity but retains structures that make it useful for immunization of research animals or stimulation of immune cells in vitro.

How do Toxoids Impact the Immune Process?

To understand how some List Labs products work, an overview of the immune process is helpful. During the course of a day, we frequently touch, ingest, or breathe in something that has potential to harm the body. Our cells react to this invader: is this a threat, or not, and if so, how serious is the threat?

What is the Innate Immune Response?

The innate immune response is the first order of defense in the immune process. There are many different cell types in our body. Some of these cells are equipped by their structural and biochemical components to destroy dangerous microbial invaders–pathogens–quickly. The inflammation that we experience from minor infections is often a sign of this process as cells from the blood destroy the pathogen. This happens quickly, within hours.

What is the Adaptive Immune Response?

Another cellular response system requires a longer time to react to the threat. These cells react by changing from an inactive form to one that will start a more complex defensive process: this is the second step, the adaptive immune response. There are two different classes of cells that comprise the adaptive immune response; they differ by the structures that give them their ability to bind antigens– the invading bacteria and viruses. Both these cells are called lymphocytes; individually, they are the B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Both originate from stem cells in the bone marrow; B and T refer to the place in the body where they mature. T-cells mature in the thymus into several subclasses of T-cells that circulate in the blood and lymph. “Killer” T-cells recognize foreign antigens on cell surfaces (e.g. from viral infection or malignancy). “Helper” T-cells induce B-cells to produce antibodies. “Suppressor” T-cells dampen or regulate the immune response to prevent over-reaction. B-cells mature in the bone marrow and migrate to secondary lymphoid tissues (e.g. spleen and lymph nodes). When they encounter foreign antigens and/or helper T-cells, they are stimulated to divide and expand clonally to produce antibodies and differentiate into plasma cells.

What is Immune Memory?

After the B and T-lymphocytes react to an antigen, two results are possible. The first, and desirable result, is that the invader is identified and defeated, leaving behind what might be called its criminal record: immune memory. When the antigen comes creeping back in the future, the adaptive immune system recognizes it and attacks. The second possibility is an over-reaction and lack of cessation of the adaptive immune process that is harmful to the body: an autoimmune condition.

Antigens, Epitopes and Vaccines

Where do vaccines come into this process? An antigen is a substance that causes the body to mount an immune response against it. Antigens include toxins, bacteria, viruses, or other substances that the body recognizes as foreign or not “self”. Vaccines have structural features similar to structures of the toxin or invading pathogen that can elicit adaptive immunity.

An epitope is a specific molecular region on the surface of an antigen, typically one of many on the antigen, that elicits an immune response and is capable of binding with the specific antibody produced by the response. A toxin has many epitopes that can be recognized by the immune response. The epitopes that are required for toxicity have been altered chemically in toxoids or by specific genetic mutations in inactive mutants; however, many epitopes are retained and can stimulate an adaptive or memory immune response that will be effective against the toxin.

Toxins and Toxoid Products for Research

Below is a list of toxin and toxoid or inactive mutant pairs of products available to support your research.

Toxin and product numbers	Toxoid	Inactive Mutant
Botulinum Neurotoxin Type A from Clostridium botulinum – 130A, 130B, 9130A	133L
Botulinum Neurotoxin Type B, Nicked, from Clostridium botulinum – 136A, 136B	139
Toxin A from Clostridium difficile – 152C	153
Toxin B from Clostridium difficile – 155A, 155B, 155L	154A
Diphtheria Toxin, Unnicked, from Corynebacterium diphtheriae – 150	151	149
Enterotoxin Type B from Staphylococcus aureus – 122	123
Tetanus Toxin from Clostridium tetani – 190A, 190B	191A, 191B

By: Rachel Berlin, Marketing Manager

List Labs is proud to be exhibiting at ASM Biothreats February 12-14th. The conference will be held in Baltimore, Maryland at the Hilton Hotel.

Thought leaders in academia, industry and government will gather to present and discuss the latest developments in the emerging field of biothreats. This year’s conference has an expanded program to include tracks on high consequence pathogen research, biological threat reduction, product development, and policy.

List Labs will be exhibiting in booth #29 and Nancy Shine will be presenting her poster on Sensitive Detection of Anthrax Lethal Factor in Plasma Using a Specific Biotinylated Fluorogenic Substrate during poster session 1 on Wednesday, February 14th from 10:30 AM- 11:30 AM in space #020. Come learn about our products that assist in the biological threat reduction such Botulinum Neurotoxins, Anthrax Lethal Factor, FRET Peptides, Shiga Toxins, Tetanus Toxins, and more! All of our research reagents are available for purchase on our website.

Visit Nancy and Karen in the List Labs booth #29, or contact us to schedule a time to meet with them at the show. Click here for more information or to register for this conference.

By: Rachel Berlin, Marketing Manager

The List Labs website hosts a library of scientific article abstracts related to the research performed using our products called the Citations Page. Visitors can search this library to learn how others have used List Labs’ reagents in their research. This valuable resource is updated monthly with new articles from a wide variety of publications. Check out a few recent articles below:

Botulinum Neurotoxin

Carrier Proteins

Clostridium difficile toxin

Lipopolysaccharide (LPS)

Diphtheria toxin

Don’t see the reagent you’re interested in? You can search the citations by product, year, publication, or by the type of cell, animal, assay, protein or research. Check it out today!

Nancy Shine, PhD, Director R&D, List Labs and author of posters

Over 20 Scientific Posters Available on our website

Scientific posters are a great way to visually display complex scientific issues. List Labs has a large list of scientific posters published on our website under the specific products they pertain to. We have been getting a lot of requests lately to compile a list of all of our published posters into one place. Please see below for a comprehensive list of all List Labs’ scientific posters to date.

Click on the one you are interested in to check it out.

Cholera Toxins

HPLC Method to Assay the ADP-Ribosyltransferase Activity of Cholera Toxin

Botulinum Toxins

Anthrax Toxins

By:
Dom C. Ouano, Marketing Associate
Debby Renshaw, Shipping Manager
Kim Krause, Laboratory Support Supervisor

Below is a list of recommended steps on handling List Labs products upon receiving them. It should be noted that these are simply our own suggestions. If your institution has a standard protocol in place, we ask that you follow said standard protocol.

As always, use caution, wear the proper personnel protection equipment, and follow safety policies of your institution, and local, state, and federal regulations when handling List Labs products.

These steps can also be found on YouTube.

How to Open the Paint-Can-Style Bottle-In-Can Units from HAZMATPAC:

Some List Labs bacterial toxins are considered Dangerous Goods. These DG’s, as they are called, are packaged with an extra layer of security: HAZMATPAC‘s Bottle-In-Can Unit. This United Nations approved security canister features a patented locking ring for additional closure. Here’s how to open it.

1) Use your hand to grasp the outer edge of the patented locking ring. Pull upwards using light to moderate force. Do not cut the locking ring. There is no need for tools or sharp objects. This step is very easy to perform with your hands.

2) Once the locking ring is removed, we recommend using either a paint can opener or a flat-head screwdriver. To open the canister itself, insert the tip under the outer lip of the lid. Pry upwards using light force.

3) Repeat this prying process clockwise or counterclockwise, according to your comfort, until the lid is fully dislodged from the canister.

4) Dispose of the locking ring and the canister according to appropriate regulations.

More information on these cans can be found at www.HAZMATPAC.com.

How to Open Vials:

1) Use pliers, forceps, hemostat, or an equivalent tool to lift the center tab.

2) Slowly peel back the tab. Gently continue pulling the tab until the crimped metal seal is broken. Remove the metal seal.

3) Use forceps or equivalent tool to slowly and gently lift and remove the rubber cap.

4) Dispose of metal seals, rubber caps, and vials according to appropriate regulations.

We hope that helps. Please refer to our support portal and knowledge base should you need any other technical assistance.