RESUMEN
Extracytoplasmic (ECF) σ factors, the largest class of alternative σ factors, are related to primary σ factors, but have simpler structures, comprising only two of six conserved functional modules in primary σ factors: region 2 (σR2) and region 4 (σR4). Here, we report crystal structures of transcription initiation complexes containing Mycobacterium tuberculosis RNA polymerase (RNAP), M. tuberculosis ECF σ factor σL, and promoter DNA. The structures show that σR2 and σR4 of the ECF σ factor occupy the same sites on RNAP as in primary σ factors, show that the connector between σR2 and σR4 of the ECF σ factor-although shorter and unrelated in sequence-follows the same path through RNAP as in primary σ factors, and show that the ECF σ factor uses the same strategy to bind and unwind promoter DNA as primary σ factors. The results define protein-protein and protein-DNA interactions involved in ECF-σ-factor-dependent transcription initiation.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Mycobacterium tuberculosis/genética , Factor sigma/genética , Transcripción Genética , Proteínas Bacterianas/biosíntesis , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Sitios de Unión , Cristalografía por Rayos X , ADN Bacteriano/metabolismo , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , Regulación Bacteriana de la Expresión Génica , Modelos Moleculares , Mycobacterium tuberculosis/metabolismo , Regiones Promotoras Genéticas , Dominios y Motivos de Interacción de Proteínas , Estructura Terciaria de Proteína , Factor sigma/química , Factor sigma/metabolismo , Factor sigma/farmacologíaRESUMEN
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is characterized by a severe idiosyncratic reaction including rash and fever, often with associated hepatitis, arthralgias, lymph node enlargement, or hematologic abnormalities. The mortality rate is approximately 10%, primarily owing to liver failure with massive or multiple disseminated focal necrosis. Here, we report a case of a 14-year-old girl treated with vancomycin because of a wound infection by methicillin-resistant Staphylococcus aureus, who presented with non-specific symptoms, which progressed to acute liver failure, displaying the hallmarks of DRESS syndrome. With the presence of aggravated hepatic encephalopathy and azotemia, the patient was refractory to medical treatments, she received a living-donor liver transplantation, and a cure was achieved without any sign of recurrence. Vancomycin can be a cause of DRESS syndrome. A high index of suspicion and rapid diagnosis are necessary not to miss this potentially lethal disease.