A novel mechanism of translational regulation in bacteria: de-repression of non-canonical start codons in response to oxidative stress

被称为链霉菌的无害土壤细菌对人类福利至关重要，因为它们是医生用于治疗传染病的绝大多数抗生素的来源，也为我们提供了许多其他药物，例如用于治疗癌症和帮助器官移植患者。我们已经确定了一种主调节因子（称为“转录因子”），它可以切换这些有用细菌的遗传机制，使它们能够在称为活性氧的有毒分子（一种称为“氧化应激”的条件）存在下生存。这项工作的目的是找出这个主调节器的活性是如何在分子水平上控制的。我们还知道，同样的主调节器控制着病原体结核分枝杆菌和白喉棒状杆菌对氧化应激的抵抗力，这两种细菌分别导致致命的结核病和白喉。这一点很重要，因为白色血细胞摄取致病菌，并将它们暴露于活性氧物质中以杀死它们，因此致病菌如M.结核和C.白喉抵抗这种氧化杀伤对人类健康潜在地重要。

The harmless soil bacteria called streptomycetes are vital to human welfare because they are the source of the vast majority of antibiotics used by doctors to cure infectious diseases, as well as providing us with numerous other medicines used, for example, to treat cancer, and to help organ transplant patients. We have identified a master regulator (called a 'transcription factor') that switches the genetic machinery of these useful bacteria to allow them to survive in the presence of toxic molecules called Reactive Oxygen Species (a condition called "oxidative stress"). The aim of this work is to find out exactly how the activity of this master regulator is controlled at the molecular level. We also know that this same master regulator controls resistance to oxidative stress in the pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae, the bacteria that cause the fatal diseases tuberculosis and diphtheria, respectively. This is important because white blood cells ingest pathogenic bacteria and expose them to Reactive Oxygen Species in order to kill them, and so the mechanisms by which disease-causing bacteria like M. tuberculosis and C. diphtheriae resist this oxidative killing are potentially important to human health.