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El parasitismo intracelular por Histoplasma capsulatum: virulencia fúngica y dependencia del calcio
T S Sebghati1, J T Engle, W E Goldman
1Department of Molecular Microbiology, Campus Box 8230, Washington University School of Medicine, St. Louis, MO 63110, USA.
Science (New York, N.Y.)
|November 18, 2000
Resumen
Las levaduras Histoplasma capsulatum requieren calcio para el crecimiento y la virulencia. La interrupción del gen de la proteína de unión al calcio 1 (CBP1) impidió el crecimiento de hongos en condiciones de bajo contenido de calcio y redujo la gravedad de la enfermedad en un modelo de ratón.
Área de la Ciencia:
- La micología de la micología.
- Enfermedades infecciosas Enfermedades infecciosas.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Histoplasma capsulatum causa la enfermedad respiratoria por hongos más común en los EE.UU.
- Este hongo dimórfico cambia de moho del suelo a levadura parásita después de la inhalación.
- Solo la forma de levadura prospera en entornos con bajo contenido de calcio y segrega una proteína que se une al calcio (CBP).
Objetivo del estudio:
- Para investigar el vínculo entre la limitación del calcio y las capacidades parasitarias de H. capsulatum.
- Para interrumpir el gen CBP1 en H. capsulatum y evaluar su impacto en el crecimiento fúngico y la virulencia.
Principales métodos:
- Se utilizó un plásmido lineal telomérico para interrumpir el gen CBP1.
- Se empleó una estrategia de selección genética en dos pasos para la interrupción de genes.
- Las levaduras mutantes cbp1 fueron probadas para el crecimiento en condiciones limitadas de calcio.
- Se evaluó la destrucción y la proliferación de macrófagos en un modelo de infección de ratón.
Principales resultados:
- Las levaduras mutantes cb p1 no pudieron crecer cuando se les privó de calcio.
- Las levaduras mutantes cb p1 exhibieron una capacidad reducida para destruir los macrófagos in vitro.
- La progresión de la infección pulmonar se vio significativamente afectada en el modelo de ratón con el mutante cb p1.
Conclusiones:
- La proteína de unión al calcio 1 (CBP1) es esencial para el crecimiento de la levadura H. capsulatum en condiciones limitantes de calcio.
- CBP1 juega un papel crítico en los mecanismos parasitarios intracelulares de H. capsulatum, incluida la destrucción de los macrófagos y la virulencia.
- Dirigirse a CBP1 puede representar una nueva estrategia terapéutica para la histoplasmosis.
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