RESUMO
Long QT and short QT syndromes (LQTS and SQTS) are cardiac repolarization abnormalities that are characterized by length perturbations of the QT interval as measured on electrocardiogram (ECG). Prolonged QT interval and a propensity for ventricular tachycardia of the torsades de pointes (TdP) type are characteristic of LQTS, while SQTS is characterized by shortened QT interval with tall peaked T-waves and a propensity for atrial fibrillation. Both syndromes represent a high risk for syncope and sudden death. LQTS exists as a congenital genetic disease (cLQTS) with more than 700 mutations described in 12 genes (LQT1-12), but can also be acquired (aLQTS). The genetic forms of LQTS include Romano-Ward syndrome (RWS), which is characterized by isolated LQTS and an autosomal dominant pattern of inheritance, and syndromes with LQTS in association with other conditions. The latter includes Jervell and Lange-Nielsen syndrome (JLNS), Andersen syndrome (AS), and Timothy syndrome (TS). The genetics are further complicated by the occurrence of double and triple heterozygotes in LQTS and a considerable number of nonpathogenic rare polymorphisms in the involved genes. SQTS is a very rare condition, caused by mutations in five genes (SQTS1-5). The present mutation update is a comprehensive description of all known LQTS- and SQTS-associated mutations.
Assuntos
Síndrome do QT Longo/genética , Mutação , Proteínas de Ancoragem à Quinase A/química , Proteínas de Ancoragem à Quinase A/genética , Anquirinas/química , Anquirinas/genética , Arritmias Cardíacas/genética , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/genética , Caveolina 3/química , Caveolina 3/genética , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/genética , Genótipo , Humanos , Canais Iônicos/química , Canais Iônicos/genética , Proteínas de Membrana/química , Proteínas de Membrana/genética , Proteínas Musculares/química , Proteínas Musculares/genética , SíndromeRESUMO
Nisin is a natural bacteriocin produced commercially by Lactococcus lactis and widely used in the food industry as a preservative because of its broad host spectrum. Despite the low productivity and troublesome fermentation of L. lactis, no alternative cost-effective host has yet been found. Bacillus subtilis had been suggested as a potential host for the biosynthesis of nisin but was discarded due to its sensitivity to the lethal action of nisin. In this study, we have reevaluated the potential of B. subtilis as a host organism for the heterologous production of nisin. We applied transcriptome and proteome analyses of B. subtilis and identified eight genes upregulated in the presence of nisin. We demonstrated that the overexpression of some of these genes boosts the natural defenses of B. subtilis, which allows it to sustain higher levels of nisin in the medium. We also attempted to overcome the nisin sensitivity of B. subtilis by introducing the nisin resistance genes nisFEG and nisI from L. lactis under the control of a synthetic promoter library.