کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2039975 1073092 2016 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ergothioneine Maintains Redox and Bioenergetic Homeostasis Essential for Drug Susceptibility and Virulence of Mycobacterium tuberculosis
ترجمه فارسی عنوان
ارگوتیونین دارای رژیم غذایی ریشه و هوموستاز بیوانرژیک برای حساسیت و ابتلا به بیماری میکوباکتریوم توبرکلوزیس
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی


• WhiB3 regulates EGT production and maintains bioenergetic homeostasis in Mtb
• EGT modulates drug sensitivity and protects Mtb from diverse oxidative stressors
• EGT is essential for Mtb survival in macrophages and in mice

SummaryThe mechanisms by which Mycobacterium tuberculosis (Mtb) maintains metabolic equilibrium to survive during infection and upon exposure to antimycobacterial drugs are poorly characterized. Ergothioneine (EGT) and mycothiol (MSH) are the major redox buffers present in Mtb, but the contribution of EGT to Mtb redox homeostasis and virulence remains unknown. We report that Mtb WhiB3, a 4Fe-4S redox sensor protein, regulates EGT production and maintains bioenergetic homeostasis. We show that central carbon metabolism and lipid precursors regulate EGT production and that EGT modulates drug sensitivity. Notably, EGT and MSH are both essential for redox and bioenergetic homeostasis. Transcriptomic analyses of EGT and MSH mutants indicate overlapping but distinct functions of EGT and MSH. Last, we show that EGT is critical for Mtb survival in both macrophages and mice. This study has uncovered a dynamic balance between Mtb redox and bioenergetic homeostasis, which critically influences Mtb drug susceptibility and pathogenicity.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 14, Issue 3, 26 January 2016, Pages 572–585
نویسندگان
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