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Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
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Un complejo de hierro derivado de la sintetasa peptídica no ribosómica (((III) del hongo patógeno Aspergillus
Wen-Bing Yin1, Joshua A Baccile, Jin Woo Bok
1Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Wisconsin 53706, USA.
Journal of the American Chemical Society
|January 31, 2013
Resumen
Los investigadores identificaron hexadehidro-astecromo (HAS), una pequeña molécula de hongos, como un factor de virulencia clave en el Aspergillus fumigatus. La activación de su grupo genético aumentó significativamente la gravedad de la infección por hongos y la mortalidad en ratones.
Área de la Ciencia:
- Microbiología Microbiología.
- La micología de la micología.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Las moléculas pequeñas (SM) son factores cruciales de virulencia en los microbios patógenos, pero la mayoría permanecen sin caracterizar.
- Los datos genómicos sugieren un vasto repertorio inexplorado de SM microbianas.
Objetivo del estudio:
- Para identificar la función de los grupos de genes crípticos en la virulencia microbiana.
- Para caracterizar nuevas moléculas pequeñas producidas por Aspergillus fumigatus.
Principales métodos:
- Análisis de microarrays de la expresión génica.
- Metabolomía comparativa de las cepas de hongos mutantes (sobreexpresión y knockout).
- Identificación de pequeñas moléculas y vías biosintéticas.
Principales resultados:
- Identificó hexadehidro-astecromo (HAS), un complejo de hierro derivado del triptófano, ya que el producto principal de la criptografía tiene un grupo de genes de péptido sintetasa no ribosómica (NRPS).
- La activación del clúster ha llevado a un aumento de la virulencia y la mortalidad fúngicas en un modelo de ratón.
- Elucidó una vía biosintética propuesta para HAS y descubrió el diálogo cruzado con la biosíntesis de fumitremorgina.
Conclusiones:
- El hexadehidro-astecromo (HAS) es un importante factor de virulencia en el Aspergillus fumigatus.
- El grupo de genes NRPS de has es crítico para la producción de HAS y la patogenicidad fúngica.
- Comprender las SM microbianas y sus vías es esencial para desarrollar nuevas estrategias terapéuticas.
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