The origin of businesses is often an interesting story. List Biological Laboratories is no exception. The company was founded in 1978 by Linda Shoer. Linda was an entrepreneurial scientist in Silicon Valley, who’d been relocated with her husband from Boston. She had an idea for a company and leveraged an initial order into a loan from a bank, fearless that her vision would be successful. That order and loan served as the starting point for List Laboratories. The first product was a Cholera Toxin.

List Labs Develops Full Range of Bacterial Toxins and Contract Manufacturing Services

Linda had a clear plan for the company and it involved the development of a product line devoted exclusively to Bacterial Toxins and related products. List Labs was the first to commercialize many bacterial toxins for research including C. difficile Toxins and Pertussis Toxins.

Linda was well connected and comfortable networking with colleagues and proposing new business ideas or ventures.  She got the company involved in contract manufacturing and consulting early on. In the 90’s List Labs was instrumental in the manufacturing of a very popular injectable consumer product to smooth facial wrinkles.   Upon her death, she left the business to the current management team; a team that has now worked together for over 20 years.

List Labs – Still Women-Owned and Cutting Edge

Shoer’s presence is still strongly felt and the company has always remained a women owned and operated business. In an era of takeovers and transition, List Laboratories has remained true to its founding and focus. Today, the List Labs catalog offers over 100 products including Toxins, Peptides, Antibodies and Lipopolysaccharides. Many of the employees have worked together for decades.

In 2008, the company built out a new lab, complete with state of the art equipment.   List has produced several batches of high purity proteins used to test vaccines. Additionally, the company specializes in the production, shipment and handling of dangerous goods. In the last several years List Labs has worked on a variety of microbiome projects, custom fills, development work and special Select Agent projects on various subtypes of Botulinum Toxin. We have also provided GMP product for many phase 1 and 2 clinical trials. We enjoy the variety of work and welcome inquiries from new customers.  

Today, List Labs takes great pride in its reputation for high quality products and exceptional customer service. The company works with businesses and organizations worldwide on custom projects or contract manufacturing opportunities as well as selling a broad array of toxins and related products. List Labs heart is in the science and the discovery of innovative solutions. Their office is located in Campbell, CA, in the Silicon Valley. If you have questions about any of our products or services, contact us today!

Volume Discounts on Toxins and Reagents

List Laboratories has been in business since 1978.  We’ve been providing our customers with quality toxins and custom manufacturing services for decades.    We want to make it easier for everyone within your company to purchase and receive the best value for those purchases. We have recently begun a volume discount program starting at 10 vials or orders exceeding $2500.  If you have a purchasing contact or team leader you’d like to share this information with, please pass it on.

Bulk and custom orders

We also offer some of our products in bulk.  If your research or project dictates a large quantity of our product, please contact us at sales@listlabs.com and let us know the amount required and we’ll work with you to provide the best sizes  and solution possible.  Bulk orders are also eligible for volume discounts. 

 

 

What is Lipopolysaccharide (LPS) and How Does it Function?

Lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, is a potent stimulator of the vertebrate innate immune system.  This innate immune system, mediated by macrophages and dendritic cells, generates a rapid response to infectious agents.  Structural patterns common to diverse LPS molecules are recognized by Toll-like receptors (TLR) and accessory proteins in serum.  LPS released from bacterial membranes is bound to LPS binding protein (LBP) in serum, transferred to CD 14, an LPS receptor glycoprotein, and presented to the TLR-4-MD-2 complex, stimulating production of cytokines.

The Role of LPS in Stimulating the Innate Immune System

LPS has a wide range of uses in research and drug development.  It may be used to stimulate immune cells and investigate the innate immune response.  In drug development, structurally modified LPS forms, such as Lipid A, have been used as vaccine adjuvants.  LPS-derived oligosaccharides have been conjugated to carrier proteins in the development of LPS containing human vaccines.

Applications of LPS in Research and Drug Development

On the other side of the spectrum of uses, LPS stimulation of the inflammation cascade is the cause of sepsis; thus, LPS and the triggered signaling pathways which lead to production of cytokines are targets for drug development.

New LPS Products from List Labs for Immunology Research

List Labs provides LPS types referenced in the studies below, E. coli O111:B4, Product # 421 and E. coli O55:B5, Product # 423.  We have also added a highly purified LPS from E. coli O113, Product #433, a valuable tool in immunology research.  Additionally, to support work with whooping cough vaccines, we now provide LPS from Bordetella pertussis, Product #400.  New product descriptions follow:

#433, HPT™ LPS, highly purified from Escherichia coli O113

HPT^TM Lipopolysaccharide (LPS) serotype O113, Highly Purified Toxin, is produced by methods ensuring the greater purity of the product.  This process uses a hot phenol extraction and proprietary chromatographic methods that effectively remove traces of protein and nucleic acid while maintaining consistently high activity reported in units of endotoxin.  Removal of these intrinsic proteins is important in that they may activate TLR 2 if present.  If there is any concern that signaling pathways are triggered by protein contaminants, this is a good LPS to use.  This LPS type was used for the National Reference Endotoxin and for the Second International Standard for Endotoxin.

#400, HPT™ LPS, highly purified from Bordetella pertussis strain 165

List Labs has developed new products in the Bordetella pertussis family due to the whooping cough outbreaks and the renewed interest in evaluation of vaccines.  B. pertussis LPS, product # 400, is isolated from native cultures of B. pertussis strain 165, and as such has an abbreviated structure, comprised of lipid A and a core oligosaccharide without an O-specific polysaccharide side chain.  In isolated B. pertussis LPS, some congeners have a trisaccharide in place of the O-chain and some do not.  HPT^TM, Highly Purified Toxin, is prepared by hot phenol extraction and proprietary chromatographic methods that effectively remove traces of protein and nucleic acid while maintaining a consistently high concentration of endotoxin units.

For more information on LPS from List Labs click here.

Use our useful Citation Finder to see List Labs lipopolysaccharides used in research.

Other citations include:

Kubler-Kielb J (2011) Conjugation of LPS-Derived Oligosaccharides to Proteins Using Oxime Chemistry. Bioconjugation Protocols, Methods in Molecular Biology 751:317-327. PMID: 21674340.

To determine if a potential drug could attenuate the consequences of exposure to LPS, a mouse model of LPS induced sepsis was created through injection of 10 mg/kg E. coli O111:B4 LPS.

Chang Y-C,Tsai M-H, Sheu W, Hsieh S-C and Chiang A-N (2013) The Therapeutic Potential and Mechanisms of Action of Quercetin in Relation to Lipopolysaccharide-Induced Sepsis In Vitro and In Vivo. PLoS One 8(11):e80744. PMC3834323.

In a study of the activation of coagulation, Pawlinski et al created a mouse model of endotoxemia with a single intraperitoneal injection of 5 mg/kg of E. coli O111:B4 LPS.

Pawlinski R, Wang JG, Owens AP 3rd, Williams J, Antoniak S, Tencati M, Luther T, Rowley JW, Low EN, Weyrich AS and Mackman N (2010) Hematopoietic and Nonhematopoietic Cell Tissue Factor Activates the Coagulation Cascade in Endotoxemic Mice. Blood 116(5):806–814. PMC2918334.

LPS induces a model of inflammatory pain in the mouse paw.  With the use of mutant mice, Calil et al were able to identify the signaling pathway involved in this pain model.

Calil IL, Zarpelon AC, Guerrero AT, Alves-Filho JC, Ferreira SH, et al. (2014) Lipopolysaccharide Induces Inflammatory Hyperalgesia Triggering a TLR4/MyD88-Dependent Cytokine Cascade in the Mice Paw. PLoS ONE 9(3):e90013. PMC3940714.

Mühlbauer et al carried out experiments in cell culture using 0.5 to 1 µg/ml of E. coli O111:B4 to demonstrate the induction of the intracellular pattern recognition receptor Nod2.

Mühlbauer M, Cheely AW,Yenugu S and Jobim C (2008) Regulation and Functional Impact of Lipopolysaccharide Induced Nod2 Gene Expression in the Murine Epididymal Epithelial Cell Line PC1. Immunology 124:256-264. PMC2566630.

Systemic administration of LPS exacerbates the formation of brain lesions in brains of mice.  These lesions play a key role both in acute brain disorders such as stroke, traumatic brain injury, and in chronic neurodegenerative disorders such as Alzheimer disease, Parkinson disease, or amyotrophic lateral sclerosis.

Degos V, Peineau S, Nijboer C, Kaindl AM, Sigaut S, Favrais G, Plaisant F, Teissier N, Gouadon E,Lombet A, Saliba E,Collingridge GL, Maze M, Nicoletti F,  Heijnen C,  Mantz J, Kavelaars A, and Gressens P (2013) GRK2 and Group I mGluR Mediate Inflammation-Induced Sensitization to Excitotoxic Neurodegeneration. Ann Neurol. 73(5):667-678. PMC3837433.

 

What is Clostridium Difficile?

Clostridium difficile is the causative agent of antibiotic-associated diarrhea and pseudomembranous colitis.  It produces two major exotoxins, Toxin A and Toxin B; however, about 10% of strains isolated from patients with colitis also contain genes, coding for a unique ADP-ribosylating toxin, CDT Binary Toxin. Additionally, Clostridium difficile produces and secretes a glutamate dehydrogenase (cdGDH).

List Labs offers four new products in the C. difficile family

New product offerings from List Labs cover other proteins produced concurrently with the exotoxins.  These proteins are valuable as alternate markers allowing more sensitive or more accurate determination of C. difficile infections (CDI).

These new products, all related to C. difficile, will be of interest to diagnostic developers, vaccine manufacturers, as well as, to those doing research in infectious diseases.  List Labs is notably offering antigens and antibodies for two C. difficile proteins which are present in C. difficile infections.  These products add to our C. difficile reagents which also include the main virulence factors Toxin A and Toxin B, and the antibodies: Goat Anti-Toxin A, Chicken Anti-Toxin B and Chicken Anti-Toxin B.

The first two products are components of CDT Binary Toxin, an ADP-ribosyltransferase.  This toxin is composed of two independently produced components, the enzymatic subunit A, CdtA, and the binding and translocation subunit B, CdtB, which mediates cell entry of CdtA.  CDT Binary Toxin causes depolymerization of the actin cytoskeleton and formation of microtubule-based membrane protrusions,resulting in cell rounding and cell death, and it is suggested to be involved in enhanced bacterial adhesion and colonization of hypervirulent C. difficile strains.  The cell surface receptor has been identified as lipolysis stimulated lipoprotein receptor (LSR).

CDT Binary Toxin, A Subunit (CDTa), Product # 157, is recombinantly expressed in E. coli and purified using affinity chromatography.  The affinity tag has subsequently been cleaved from the protein prior to packaging.  Binary toxin A subunit has been tested in an in vitro ADP-ribosylation assay.  It is non-toxic and unable to penetrate cells in the absence of the B subunit binding and translocation domain.  Expression and purification of the A subunit from a recombinant setting ensures that there is no possible contamination with the B subunit.

1)      #157A, Binary Toxin from Clostridium difficile A Subunit 20 ug, price $350

CDT Binary Toxin, B Subunit (CDTb), Product # 158, is recombinantly expressed in E. coli, purified using affinity chromatography and the affinity tag cleaved.  Prior to packaging, the B subunit is nicked with trypsin for activation.  The B subunit of the Binary Toxin is non-toxic, and does not contain any enzymatic activity.

2)      #158A, Binary Toxin from Clostridium difficile B Subunit 40 ug, price $350

 The next products are chicken antibodies: Chicken Anti-CDT Binary B subunit antibodies, with and without biotin.  Antibodies have been raised against C. difficile Binary Toxin B Subunit and affinity purified on an antigen column, Product # 758.  These antibodies are suitable for use in Western Blot assays and ELISAs as an effective probe for C. difficile Binary Toxin B Subunit.  Additionally, purified antibody has been labeled with biotin, Product # 759, providing antibodies for both capture and detection.

3)      #758A, Anti – C. difficile Binary Toxin B Subunit (Chicken IgY) 0.1 mg, price $290

4)      #759A, Biotinylated Anti – C. difficile Binary Toxin B Subunit (Chicken IgY) 0.1 mg, price $315

Usage

Use of CDT on subconfluent Caco-2 cells is described by Schwan et al, 2009.  Toxin –induced cellular processes were observed on these cells after one hour treatment with CDT Binary Toxin, a mixture of 20 ng/ml of CDTa and 40 ng/ml of CDTb.

Use our new Citations Finder to see additional citations of how C. Difficile from List Labs has been used in research.

Reference

1. Schwan C., Stecher B., Tzivelekidis T., van Ham M., Rohde M., Hardt WD., Wehland J., Aktories K., (2009) Clostridium difficile Toxin CDT Induces Formation of Microtubule-Based Protrusions and Increases Adherence of Bacteria. PLoS Pathog 5(10): e1000626. PMID: 19834554

Since 1978, List Labs has been known as a manufacturer of fine research reagents.  Located in Silicon Valley, our company is woman-owned and managed.  We enjoy long-standing relationships with many researchers who have used our products for decades, bringing the continuity of List’s products along with them as they move up to new career opportunities.

Full Range of Contract Manufacturing Services

In addition to our catalog products, we offer a full complement of professional services, including:  GMP Contract Manufacturing, Production of Live Biotherapeutics, Contract Research, Formulation/Lyophilization and Navigating both Toxin Compliance, and Regulatory Requirements.  Our manufacturing  and biocontainment experience, and our well-established record of working with partners to successfully bring products to market makes us a great service provider to companies of all sizes.

Full cGMP Facility

List Labs offers a full cGMP facility, and labs designed to meet the most exacting requirements including biocontainment. See our equipment list here. Our scientists are experts at working with pharma, start ups, government and entrepreneurs to further their research, to produce API , and to perform testing.  We extend our clients’ capabilities!

Start Your Partnership with List Labs Today!

If you have a project and you’d like to work with a partner who can work independently or as a member of your team, has their own state of the art lab suite, understands key requirements and navigating regulations implicit in toxin production, then contact us to discuss your needs.

List Labs has a compelling history of successful partnerships, ask us to tell you how we’ve helped bring major products to market and why we are a critical link to the scientific success of the work we do.  Check out Citations where our products have been used in research.

We will be attending BIO2014 in San Diego June 23-26 where we will be meeting with companies who have an interest in our wide range of Professional Services.  We are also happy to arrange a meeting and tour at our California office. Just email us.

 

What Are Toxin Neutralization Assays & How Do They Work?

For clinical detection or vaccine testing, it is hard to beat a toxin neutralization assay.  Toxin neutralization assays (TNA) assess the ability of antibodies to protect cells in culture from the cytotoxic affect of the specific toxins.  Interestingly, these assays may be used for sensitive and reliable testing for disease states where toxins are involved, as well as for development of vaccines to treat infectious disease.  In TNA testing, potential sources of toxin and antibodies are combined and applied to cell culture in a series of dilutions.  Excess toxin in the sample, not neutralized by the antibody, will kill the cells, the amount of excess toxin determined by the dilution of the sample which will cause a defined amount of cell death.  The end point in such assays is cell viability, and this may be visualized by several different methods.  A commonly used method is to visualize viable cells through metabolism of a staining reagent; the intensity of the developed color is directly proportional to the percent of remaining cell viability.  TNA assays can also be used as a definitive identification of the causal agent of the disease.

TNA Assays for Clostridium Difficile Diagnosis

Cytotoxin neutralization (CTN or TNA) assays have great value in the specific diagnosis of C. difficile.  Laboratory diagnosis is described by Alfa and Sepehri (Alfa, 2013).  These assays can progress through a stepwise process starting with testing for glutamate dehydrogenase (GDH) in stool from potential C. difficile infected (CDI) patients.  C. difficile GDH (cdGDH) is a highly active enzyme which can be readily detected and correlates well with C. difficile infections.  Test results that are negative for GDH can identify samples in which C. difficile is highly unlikely, whereas tests positive for this enzyme can be used to identify potential C. difficile infections.  However, since GDH is also produced by other inhabitants of the digestive tract, the presence of GDH is not conclusive evidence of C. difficile.  To take diagnosis a step farther, immunological assays for C. difficile toxins A and B are used and when positive, identify C. difficile infections.  Low sensitivity of these assays produce false negative results when only a small amount of toxin is present; this is when a TNA assay on highly sensitive cells comes into play.  Depending on the type of cell culture, it is possible to detect C. difficile toxin B at a concentration of picograms per ml.  Because cell cultures may be killed by a variety of components in a test sample, specific identity of the toxin relies on the use of standard neutralizing antibodies directed uniquely to C. difficile toxin A or B.  When the antibody protects the cells from toxin directed death, the presence of, for example, the C. difficile toxin B is shown; this is a positive indication of a CDI patient.  Toxin neutralization is a valuable assay in identifying patients infected with C. difficile and List Labs products are used in the development of these assays and subsequent testing to detect the toxins in samples.  Products available from List Lab are C. difficile toxin A, C. difficile toxin B, our new product C. difficile GDH as well as antibodies directed to these three proteins, all of which are used to perform TNA.

TNA Assays Used to Evaluate Potential Vaccines

Another equally important use of toxin neutralization is in testing for the evaluation of potential vaccines.  A paper published in 2013 by Xie et al describes a TNA developed for the evaluation of hyperimmune sera raised in animals against potential C. difficile toxin A (TcdA) and toxin B (TcdB) toxoid vaccine candidates.  The authors optimized the assay using Vero cells for detection of neutralizing antibodies and for the determination of toxin potency.

TNA Assays for Anthrax Vaccines

Similar toxin neutralization assays have been developed and optimized for anthrax vaccines.  These assays have been in use for over 10 years.  A good review of these assays using different types of cultured cells to measure antibody levels created in response to different vaccines was provided by Ngundi et al, 2010.  Anthrax toxin products available from List Labs are protective antigen (PA), lethal factor (LF), edema factor (EF), as well as the respective antibodies, all of which are used in these assays.

References:

Alfa et al (2013) Combination of culture, antigen and toxin detection, and cytotoxin neutralization assay for optimal Clostridium difficile diagnostic testing. Can J Infect Dis Med Microbiol 24(2) 89-92. PMCID 3720004

Ngundi et al (2010) Comparison of Three Anthrax Toxin Neutralization Assays. Clinical and Vaccine Immunology 17(6) 895–903. PMID: 20375243

Xie et al (2013) Development and Optimization of a Novel Assay to Measure Neutralizing Antibodies Against Clostridium difficile Toxins. Clinical and Vaccine Immunology 20(4) 517-525. PMID: 23389929

 

List Biological Laboratories, Inc. (List) actively supports and participates in the BabyBIG^® project.

What is BabyBIG^® ?

BabyBIG^® (Human Botulism Immune Globulin; BIG-IV) is a public service, not-for-profit orphan drug manufactured and distributed by the California Department of Public Health.It is the only therapy available for infants who are infected with the organism that causes botulism, a life-threatening disease.

List Labs Volunteers Donate Plasma to Support Orphan Drug BabyBIG^® 

Because List produces the botulinum toxin for research use, employees are vaccinated against the toxin, thereby producing antibodies which circulate in their plasma.  This puts List Laboratories in a rare position to help with this project.  These antibodies are donated by volunteer employees via plasmapheresis, a procedure similar to a blood donation, for a period of up to 12 weeks.  Life-saving plasma is blended and processed into the final BabyBIG^® product.  We are proud of being able to be a big part of this amazing product and effort.  There are only a handful of organizations and entities who would be able to participate at any level and over 1/3 of our employees are active donors.  We salute them and support them in their time commitment to a worthy cause.

Infant Botulism Patients Helped in a Big Way by BabyBIG^® 

Since licensure of BabyBIG^® in 2003, approximately 1100 infant botulism patients nationwide have been treated with it, thereby shortening each hospital stay by almost one month and reducing the negative impact of this disease on these young patients.  In the aggregate since licensure, treatment with BabyBIG^® has resulted in more than 65 years of avoided hospital stay and more than $100 million in avoided hospital costs.

More information about BabyBIG^® may be found on their web site www.infantbotulism.org

 

Shiga Toxins May be Purchased without Government Approval

The CDC has removed Shiga toxins (Stx1 and Stx2) from the list of materials requiring oversight.  As a result, Shiga Toxins are no longer classified as select agents and may be purchased without government approval for your research and investigative needs.   While Shiga toxins carry fewer restrictions, the interest in them and their value for research has never been higher.

Usage of Shiga Toxins in Research

As tools, these cytotoxins are valuable in studying intracellular transport within the Golgi apparatus.  They can be used to eliminate mammalian cell types with Gb3 receptors. Shiga toxins are potent virulence factors, important in human health.  They are implicated in many cases of food borne illness, estimated to affect 76 million people and cause 5,000 deaths every year in the United States alone.  Shiga toxin producing bacteria, usually Escherichia coli O157, enter the food chain through contamination, infect the gastrointestinal tract and cause diarrheal illness.  The bacteria infect the large intestine and produce Shiga toxin which crosses the gastrointestinal epithelium entering the blood stream; ultimately the toxins are responsible for organ damage.  These potent virulence factors are important targets for the development of therapies and for the detection of contamination.

Shiga toxins function by inhibiting eukaryotic protein synthesis by cleaving a specific adenine from the 28S RNA of the 60S subunit of the ribosome.  Although Shiga toxin 1 and Shiga toxin 2 share only 56% amino acid homology, making them immunologically distinct, activities of these two forms of toxin, binding affinity to Gb3 and N-glycosidase activity, appear to be identical.  In spite of these similarities, Shiga toxin 2 is more closely associated with human disease.  Although endothelial cells are the primary cell type vulnerable to shiga toxin, several other types express Gb3 receptors and are therefore potential targets.

Get Shiga Toxins for Research from ListLabs

Both Shiga 1 and Shiga 2 and mouse antibodies to the toxins are available from List Labs. You can read more about them here. At this time we are evaluating polyclonal and monoclonal antibodies that recognize all seven subtypes of Stx2 and monoclonals that recognize all subtypes of Stx1.  Look for these antibodies to appear in our future offerings.