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Objetivos de tejidos clave responsables de la letalidad inducida por la toxina del ántrax.

Shihui Liu1, Yi Zhang, Mahtab Moayeri

  • 1Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. shliu@niaid.nih.gov

Nature
|September 3, 2013
PubMed
Resumen

Las toxinas de Bacillus anthracis causan letalidad al dañar distintos tipos de células. La toxina letal del ántrax (LT) ataca las células cardíacas y vasculares, mientras que la toxina del edema (ET) afecta principalmente a las células hepáticas (hepatocitos).

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Área de la Ciencia:

  • Microbiología Microbiología.
  • Toxicología Toxicología.
  • Fisiopatología Fisiopatología.

Sus antecedentes:

  • Bacillus anthracis causa el ántrax a través de dos exotoxinas: la toxina letal (LT) y la toxina del edema (ET).
  • Los objetivos específicos de las células huésped responsables de los efectos letales de estas toxinas siguen sin identificarse.
  • La proteína de morfogénesis capilar-2 (CMG2) es un receptor conocido para estas toxinas.

Objetivo del estudio:

  • Para dilucidar los tipos de células críticas dirigidas por la toxina letal del ántrax (LT) y la toxina del edema (ET) que conducen a la mortalidad del huésped.
  • Investigar el papel del receptor de la toxina del ántrax CMG2 en la mediación de la letalidad inducida por la toxina en diferentes tipos de células.

Principales métodos:

  • Generación de ratones CMG2-nulo y CMG2-expresores específicos del tipo de célula.
  • Desafiando a estos ratones genéticamente modificados con la toxina letal del ántrax purificada (LT) y la toxina del edema (ET).
  • Evaluar la contribución de tipos celulares específicos a la mortalidad inducida por toxinas.

Principales resultados:

  • La letalidad de LT implica daño a los cardiomiocitos y las células del músculo liso vascular.
  • La letalidad inducida por ET está mediada principalmente a través de su acción sobre los hepatocitos.
  • Contrariamente a las hipótesis anteriores, la orientación de las células endoteliales por LT o ET no contribuye significativamente a la mortalidad.

Conclusiones:

  • Bacillus anthracis emplea LT y ET para inducir la letalidad del huésped mediante el daño coordinado de distintos sistemas de órganos vitales.
  • LT y ET exhiben un tropismo de tipo celular diferencial, apuntando a poblaciones celulares críticas separadas para efectos letales.
  • Las células endoteliales no son un objetivo primario para la letalidad inducida por la toxina del ántrax.