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Related Concept Videos

Lethal Alleles02:41

Lethal Alleles

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Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
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Related Experiment Video

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A High-throughput-compatible FRET-based Platform for Identification and Characterization of Botulinum Neurotoxin Light Chain Modulators
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Anthrax lethal toxin (LeTx) neutralization by PA domain specific antisera.

Monika Verma1, Nagendra Suryanarayana1, Urmil Tuteja1

  • 1Microbiology Division, Defence Research & Development Establishment, Jhansi Road, Gwalior, Madhya Pradesh, 474002, India.

Toxicon : Official Journal of the International Society on Toxinology
|September 19, 2017
PubMed
Summary

Researchers developed antibodies against protective antigen (PA) domains to neutralize anthrax lethal toxin (LeTx). Antisera targeting PA domain IV showed high efficiency in neutralizing LeTx, suggesting its therapeutic potential against anthrax.

Keywords:
Anthrax lethal toxinLethal toxin neutralizationMALDI –TOFPA domain specific antisera

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Area of Science:

  • Immunology
  • Microbiology
  • Toxicology

Background:

  • Anthrax toxicity in humans and animals is primarily caused by two exotoxins from Bacillus anthracis.
  • These exotoxins, lethal toxin (LeTx) and edema toxin (EdTx), are composed of protective antigen (PA), lethal factor (LF), and edema factor (EF).
  • PA is a crucial component for forming both LeTx and EdTx, making it a target for therapeutic interventions.

Purpose of the Study:

  • To evaluate the lethal toxin neutralization potential of polyclonal antisera generated against individual domains of the Bacillus anthracis protective antigen (PA).
  • To identify specific PA domains that elicit antibodies capable of neutralizing anthrax lethal toxin (LeTx).

Main Methods:

  • Recombinant proteins of individual PA domains were produced in E. coli.
  • Polyclonal antisera were developed in mice against these recombinant PA domains.
  • Antibody titers and isotypes were determined by ELISA, and neutralization capacity was assessed using an in-vitro cell viability MTT assay against LeTx.

Main Results:

  • Antisera were generated against four domains of the protective antigen.
  • ELISA and Western blotting confirmed antibody presence and specificity.
  • The antiserum against PA domain IV demonstrated significant efficiency in neutralizing lethal toxin (LeTx) in vitro.
  • Antisera against other PA domains showed minimal to no LeTx neutralization.

Conclusions:

  • Antibodies targeting the protective antigen domain IV show promise as a potential therapeutic agent against anthrax lethal toxin.
  • Further exploration of anti-PA domain IV antibodies is warranted for developing novel anti-anthrax therapeutics, potentially in combination with antibiotics.