Many bacteria encode biosynthetic proteins that produce a vast array of natural products. These compounds are often synthesized during host invasion as they function as virulence factors. In addition, such secondary metabolites have yielded numerous molecular scaffolds with pharmaceutical and clinical importance. The gene clusters that encode proteins responsible for synthesis of these compounds are typically silenced or “cryptic” under laboratory growth conditions, hampering discovery of novel lead compounds. We report here that MftR is a global repressor of secondary metabolite synthesis in Burkholderia thailandensis and that urate functions as a physiologically relevant inducer of gene expression. Biosynthetic gene clusters under MftR control include those associated with production of the antimicrobial bactobolins, the iron siderophore malleobactin, and the virulence factor malleilactone. MftR also controls additional genes associated with survival in a host environment, such as genes encoding components of the type III secretion system (T3SS) and proteins linked to anaerobic respiration. This observation not only has implications for understanding activation of gene regulatory networks during host invasion, but it also paves the way for isolation of novel therapeutic leads.

中文翻译：

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伯克霍尔德氏菌泰国隐性生物合成基因簇的全球觉醒

许多细菌编码产生大量天然产物的生物合成蛋白。这些化合物通常在宿主入侵期间合成，因为它们起毒力因子的作用。另外，这种次级代谢产物已经产生了许多具有药物和临床重要性的分子支架。编码负责合成这些化合物的蛋白质的基因簇通常在实验室生长条件下被沉默或“隐秘”，从而阻碍了新型先导化合物的发现。我们在这里报告，MftR是泰国伯克霍尔德菌次级代谢产物合成的全球阻遏物而尿酸盐起着基因表达的生理相关诱导物的作用。在MftR控制下的生物合成基因簇包括与抗菌素，铁铁载体铁载体和毒力因子内酯的生产相关的那些。MftR还控制与宿主环境中的生存相关的其他基因，例如编码III型分泌系统（T3SS）成分的基因和与厌氧呼吸有关的蛋白质。该观察结果不仅对理解宿主入侵期间基因调控网络的激活有重要意义，而且还为隔离新型治疗用药铺平了道路。