A Novel Surface Plasmon Resonance Biosensor for the Rapid Detection of Botulinum Neurotoxins

Patel, Kruti; Halevi, Shmuel; Melman, P.; Schwartz, John; Cai, Shuowei; Singh, Bal Ram

doi:10.3390/bios7030032

Cited by 27 publications

(23 citation statements)

References 29 publications

(30 reference statements)

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“…The toxicity of BoNTs could be known from the fact that they are 100 billion times more toxic than cyanide and million times to sarin 35 . The extreme toxicity (LD 50 ~ 1 ng/kg), unavailability of antidotes and relative ease of production contributes to their potential as powerful bioweapon agents 36 . In spite of extensive research in the field, no FDA approved treatment is yet available against botulinum neurotoxin intoxication.…”

Section: Discussionmentioning

confidence: 99%

Characterization of immune response induced against catalytic domain of botulinum neurotoxin type E

Sonkar

Chauhan

et al. 2020

Sci Rep

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Botulinum neurotoxins (Bonts) represent a family of bacterial toxins responsible for neuroparalytic disease 'botulism' in human and animals. their potential use as biological weapon led to their classification in category 'A' biowarfare agent by Centers for Disease Control and Prevention (CDC), USA. In present study, gene encoding full length catalytic domain of BoNT/E-LC was cloned, expressed and protein was purified using Ni-NTA chromatography. Humoral immune response was confirmed by Ig isotyping and cell-mediated immunity by cytokine profiling and intracellular staining for enumeration of IFN-γ secreting CD4 + and CD8 + t cells. increased antibody titer with the predominance of IgG subtype was observed. An interaction between antibodies produced against rBoNT/E-LC was established that showed the specificity against BoNT/E in SPR assay. Animal protection with rBoNT/E-LC was conferred through both humoral and cellular immune responses. These findings were supported by cytokine profiling and flow cytometric analysis. Splenocytes stimulated with rBoNT/E-LC showed a 3.27 and 2.8 times increase in the IFN-γ secreting CD4 + and CD8 + T cells, respectively; in immunized group (P < 0.05). Protection against BoNT/E challenge tended to relate with increase in the percentage of rBoNT/E-LC specific IL-2 in the splenocytes supernatant (P = 0.034) and with IFN-γ-producing CD4 + T cell responses (P = 0.045). We have immunologically evaluated catalytically active rBoNT/E-LC. Our results provide valuable investigational report for immunoprophylactic role of catalytic domain of BoNT/E. Clostridium botulinum is Gram-positive anaerobic, spore-forming bacteria that produce botulinum neurotoxins (BoNTs). Botulinum neurotoxins are considered as the most toxic substances known to humankind 1 and the causative agent of botulism 2. BoNTs are also classified by the Centers for Disease Control (CDC) as one of the highest-risk threat agents for bioterrorism ("Class A agents") 3. Botulism is characterized by flaccid paralysis induced by blockade of acetylcholine release at neuromuscular junctions that, if not treated, can be fatal 4. Traditionally, based on their antigenic properties, BoNTs are classified into 7 distinct serotypes (A-G) 5. Recently a new serotype was reported as BoNT-H 6 , it has since been disproven as a novel serotype, collective data now accurately described it as FA chimeric i.e. BoNT/F5A or BoNT/HA rather than a novel new serotype 7,8. All BoNT serotypes act through similar mechanisms on their target neuronal cells. BoNTs are synthesized as an inactive single polypeptide chain of ~ 150 kDa. It is activated after post-translational cleavage in di-chain consisting of a ~ 100 kDa heavy chain (HC) and a ~ 50 kDa light chain (LC) held together via single disulfide bond 9. Structurally, these BoNTs are composed of three functional domains of ~ 50 kDa each; receptor-binding domain (HC C), translocation domain (HC N), and catalytic domain (LC). Intoxication of BoNTs is a multistep process that initiates with the binding of HC...

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Section: Discussionmentioning

confidence: 99%

Characterization of immune response induced against catalytic domain of botulinum neurotoxin type E

Sonkar

Chauhan

et al. 2020

Sci Rep

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“…Evidence of increased sensitivity is demonstrated by the recently developed Newton Photonics SPR biosensor, which has a LoD quantified at 6.76 pg/mL (BoNT/A light chain), allowing for active toxin quantification, which is advantageous for its adoption in the pharmaceutical production sector. The SPR method has a detection time of less than 20 minutes [81].…”

Section: Methods Of Detectionmentioning

confidence: 99%

Rapid Detection of Botulinum Neurotoxins—A Review

Hobbs

Thomas

Halliwell

et al. 2019

Toxins

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A toxin is a poisonous substance produced within living cells or organisms. One of the most potent groups of toxins currently known are the Botulinum Neurotoxins (BoNTs). These are so deadly that as little as 62 ng could kill an average human; to put this into context that is approximately 200,000 × less than the weight of a grain of sand. The extreme toxicity of BoNTs leads to the need for methods of determining their concentration at very low levels of sensitivity. Currently the mouse bioassay is the most widely used detection method monitoring the activity of the toxin; however, this assay is not only lengthy, it also has both cost and ethical issues due to the use of live animals. This review focuses on detection methods both existing and emerging that remove the need for the use of animals and will look at three areas; speed of detection, sensitivity of detection and finally cost. The assays will have wide reaching interest, ranging from the pharmaceutical/clinical industry for production quality management or as a point of care sensor in suspected cases of botulism, the food industry as a quality control measure, to the military, detecting BoNT that has been potentially used as a bio warfare agent.

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“…Finally, surface plasmon resonance (SPR), an important labelfree analytical strategy, could be applied for the simultaneous sensitive detection of multiple targets with superiorities, such as good specificity, real-time monitoring, and high throughput detection (Patel et al, 2017). More recently, Wei et al developed a SPR-based aptasensor chip for the simultaneous determination of four mycotoxins with low crossreactivity (Figure 11), which has been successfully used for practical analysis in wheat and corn.…”

Section: Aptasensors For Simultaneous Multi-mycotoxins Analysismentioning

confidence: 99%

Aptamer-Based Biosensor for Detection of Mycotoxins

et al. 2020

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Mycotoxins are a large type of secondary metabolites produced by fungi that pose a great hazard to and cause toxic reactions in humans and animals. A majority of countries and regulators, such as the European Union, have established a series of requirements for their use, and they have also set maximum tolerance levels. The development of high sensitivity and a specific analytical platform for mycotoxins is much in demand to address new challenges for food safety worldwide. Due to the superiority of simple, rapid, and low-cost characteristics, aptamer-based biosensors have successfully been developed for the detection of various mycotoxins with high sensitivity and selectivity compared with traditional instrumental methods and immunological approaches. In this article, we discuss and analyze the development of aptasensors for mycotoxins determination in food and agricultural products over the last 11 years and cover the literatures from the first report in 2008 until the present time. In addition, challenges and future trends for the selection of aptamers toward various mycotoxins and aptasensors for multi-mycotoxins analyses are summarized. Given the promising development and potential application of aptasensors, future research studies made will witness the great practicality of using aptamer-based biosensors within the field of food safety.

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A Novel Surface Plasmon Resonance Biosensor for the Rapid Detection of Botulinum Neurotoxins

Cited by 27 publications

References 29 publications

Characterization of immune response induced against catalytic domain of botulinum neurotoxin type E

Characterization of immune response induced against catalytic domain of botulinum neurotoxin type E

Rapid Detection of Botulinum Neurotoxins—A Review

Aptamer-Based Biosensor for Detection of Mycotoxins

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