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Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
Published on: May 4, 2018
La degradación proteasomal del huésped genera aminoácidos esenciales para el crecimiento bacteriano intracelular
Christopher T D Price1, Tasneem Al-Quadan, Marina Santic
1Department of Microbiology and Immunology, College of Medicine, University of Louisville, KY 40202, USA.
Science (New York, N.Y.)
|November 19, 2011
Resumen
Legionella pneumophila utiliza su efector AnkB para desencadenar la descomposición de las proteínas de las células huésped, generando aminoácidos esenciales para el crecimiento bacteriano en ameba, células humanas y ratones.
Área de la Ciencia:
- Microbiología Microbiología.
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Legionella pneumophila es una bacteria intracelular que se replica dentro de una vacuola especializada (LCV).
- La membrana LCV es el objetivo de los efectores bacterianos, incluida la proteína AnkB F-box, que se ancla a través de la farnesilación del huésped.
- Comprender las estrategias de adquisición de nutrientes es crucial para controlar las infecciones por Legionella.
Objetivo del estudio:
- Para investigar el papel de AnkB en la adquisición de nutrientes para Legionella pneumophila.
- Determinar cómo la Legionella utiliza la maquinaria celular del huésped para su proliferación.
- Identificar los recursos derivados del huésped esenciales para la supervivencia bacteriana intracelular.
Principales métodos:
- Generación y análisis de un mutante nulo ankB de Legionella pneumophila.
- Evaluación de la proliferación bacteriana en las células huésped (amiba, células humanas) e in vivo (ratones).
- Los ensayos de suplementación con aminoácidos, cisteína, serina, piruvato o citrato para rescatar fenotipos mutantes.
Principales resultados:
- La degradación proteasómica del huésped de las proteínas poliubiquitinadas ligadas a Lys ((48) en el CVL, mediada por AnkB, genera aminoácidos.
- El mutante ankB exhibe graves defectos de proliferación en amebas y células humanas, que son rescatadas por la suplementación con aminoácidos.
- Los defectos de proliferación intrapulmonar del mutante ankB en ratones también se rescatan mediante la inyección de aminoácidos o cisteína.
Conclusiones:
- Legionella pneumophila secuestra activamente el sistema proteasómico del huésped para degradar las proteínas del huésped.
- Los aminoácidos generados sirven como fuentes críticas de carbono y energía para la proliferación bacteriana.
- Este mecanismo de adquisición de nutrientes se conserva en anfitriones evolutivamente distantes, lo que pone de relieve una estrategia clave de supervivencia para la Legionella.
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