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首页> 外文期刊>Applied Microbiology >Ferric Uptake Regulator Fur Coordinates Siderophore Production and Defense against Iron Toxicity and Oxidative Stress and Contributes to Virulence in Chromobacterium violaceum
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Ferric Uptake Regulator Fur Coordinates Siderophore Production and Defense against Iron Toxicity and Oxidative Stress and Contributes to Virulence in Chromobacterium violaceum

机译：Ferric摄取调节器皮草坐标，坐标生产和防御铁毒性和氧化应激，有助于紫杉杆菌的毒力

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摘要

Iron is a highly reactive metal that participates in several processes in prokaryotic and eukaryotic cells. Hosts and pathogens compete for iron in the context of infection. Chromobacterium violaceum , an environmental Gram-negative bacterial pathogen, relies on siderophores to overcome iron limitation in the host. In this work, we studied the role of the ferric uptake regulator Fur in the physiology and virulence of C. violaceum . A Δ fur mutant strain showed decreased growth and fitness under regular in vitro growth conditions and presented high sensitivity to iron and oxidative stresses. Furthermore, the absence of fur caused derepression of siderophore production and reduction in swimming motility and biofilm formation. Consistent with these results, the C. violaceum Δ fur mutant was highly attenuated for virulence and liver colonization in mice. In contrast, a manganese-selected spontaneous fur mutant showed only siderophore overproduction and sensitivity to oxidative stress, indicating that Fur remained partially functional in this strain. We found that mutations in genes related to siderophore biosynthesis and a putative CRISPR-Cas locus rescued the Δ fur mutant growth defects, indicating that multiple Fur-regulated processes contribute to maintaining bacterial cell fitness. Overall, our data indicated that Fur is conditionally essential in C. violaceum mainly by protecting cells from iron overload and oxidative damage. The requirement of Fur for virulence highlights the importance of iron in the pathogenesis of C. violaceum .IMPORTANCE Maintenance of iron homeostasis, i.e., avoiding both deficiency and toxicity of this metal, is vital to bacteria and their hosts. Iron sequestration by host proteins is a crucial strategy to combat bacterial infections. In bacteria, the ferric uptake regulator Fur coordinates the expression of several iron-related genes. Sometimes, Fur can also regulate several other processes. In this work, we performed an in-depth phenotypic characterization of fur mutants in the human opportunistic pathogen Chromobacterium violaceum . We determined that fur is a conditionally essential gene necessary for proper growth under regular conditions and is fully required for survival under iron and oxidative stresses. Fur also controlled several virulence-associated traits, such as swimming motility, biofilm formation, and siderophore production. Consistent with these results, a C. violaceum fur null mutant showed attenuation of virulence. Therefore, our data established Fur as a major player required for C. violaceum to manage iron, including during infection in the host.
机译：铁是一种高反应性金属，参与原核和真核细胞中的几种方法。在感染的背景下，宿主和病原体竞争铁。紫杉杆菌，一种环保革兰阴性细菌病原体，依靠施工电池来克服宿主中的铁限制。在这项工作中，我们研究了Ferric摄取调节器皮草在C. violaceum的生理和毒力中的作用。 δ毛突变体菌株在常规体外生长条件下显示出的生长和适应性降低，并对铁和氧化胁迫提高了高敏感性。此外，没有毛皮引起了潜水的展望山脉生产和减少游泳运动和生物膜形成。与这些结果一致，C.violateumδ毛突变体高度衰减针对小鼠的毒力和肝脏定植。相反，锰的自发性毛虫突变体仅显示了氧化胁迫的膀胱生产和敏感性，表明皮草在该菌株中保持部分官能。我们发现与阳光生物合成和推定的CRISPR-CAS基因座有关的基因的突变救出了δ毛突变体生长缺陷，表明多种毛刺工艺有助于保持细菌细胞的适应度。总的来说，我们的数据表明，皮毛在C. violateum有条件必需的主要是通过保护电池免受铁过载和氧化损伤。毛皮的要求为毒力突出了铁在C. violateum的发病机制中的重要性。It.e.，避免这种金属的缺乏和毒性，对细菌及其主持人至关重要。宿主蛋白的铁封存是对抗细菌感染的重要策略。在细菌中，Furrram吸收调节剂皮草坐标坐标几种有关基因的表达。有时，毛皮还可以调节其他几个过程。在这项工作中，我们在人体机会理性病原体紫杉杆菌中进行了毛皮突变体的深入表型表征。我们确定毛皮是在规则条件下适当增长所需的有条件基因，并且在铁和氧化应激下的存活是完全所必需的。毛皮还控制了多种毒力相关的性状，例如游泳运动，生物膜形成和阳光生产。与这些结果一致，C. violateum毛皮突变体显示出毒力的衰减。因此，我们的数据建立了毛皮作为C. violaceum来管理铁的主要球员，包括在宿主感染期间。

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