铁是所有生物体所必需的,在人类宿主中引起感染的细菌也需要亚铁离子来生长和增殖。在人体中,大多数三价铁离子(Fe3+)与铁结合蛋白如血红蛋白紧密结合,转铁蛋白,乳铁蛋白,和铁蛋白.病原菌表达高度特异性的铁摄取系统,包括铁载体和特异性受体.大多数细菌分泌铁载体,它们是低分子量的金属螯合剂,在细胞外捕获Fe3+。铁载体主要分类为儿茶酚酸盐或异羟肟酸盐。创伤弧菌,革兰氏阴性致病菌,是人类严重感染的原因,需要铁来生长。临床分离株,V.创伤M2799,分泌儿茶酚铁载体,vulnibactin,从环境中捕获三价铁离子。在我们的研究中,我们产生了编码参与外阴肌动蛋白介导的铁利用系统的蛋白质的基因的缺失突变体,如铁-外阴肌动蛋白受体蛋白(VuuA),周质外阴肌动蛋白结合蛋白(FatB),铁-外阴肌动蛋白还原酶(VuuB),和异氯酸合酶(ICS)。在低铁条件下,M2799中的铁利用需要ICS和VuuA,但替代蛋白FatB和VuB可以充当周质结合蛋白和铁螯合还原酶,分别。VatD,作为铁-异羟肟酸铁载体周质结合蛋白,显示在不存在FatB的情况下参与铁-外阴肌动蛋白摄取系统。此外,在不存在VuuB的情况下,观察到铁-异羟肟酸铁载体还原酶IutB参与了铁-外阴肌动蛋白的还原。我们认为,铁-铁载体周质结合蛋白和铁-螯合还原酶是在传染病背景下发现药物的潜在靶标。
Iron is necessary for all living organisms, and bacteria that cause infections in human hosts also need ferrous ions for their growth and proliferation. In the human body, most ferric ions (Fe3+) are tightly bound to iron-binding proteins such as hemoglobin, transferrin, lactoferrin, and ferritin. Pathogenic bacteria express highly specific iron uptake systems, including siderophores and specific receptors. Most bacteria secrete siderophores, which are low-molecular weight metal-chelating agents, to capture Fe3+ outside cell. Siderophores are mainly classified as either catecholate or hydroxamate. Vibrio vulnificus, a Gram-negative pathogenic bacterium, is responsible for serious infections in humans and requires iron for growth. A clinical isolate, V. vulnificus M2799, secretes a catecholate
siderophore, vulnibactin, that captures ferric ions from the environment. In our study, we generated deletion mutants of the genes encoding proteins involved in the vulnibactin mediated iron-utilization system, such as ferric-vulnibactin receptor protein (VuuA), periplasmic ferric-vulnibactin binding protein (FatB), ferric-vulnibactin reductase (VuuB), and isochorismate synthase (ICS). ICS and VuuA are required under low-iron conditions for ferric-utilization in M2799, but the alternative proteins FatB and VuuB can function as a periplasmic binding protein and a ferric-chelate reductase, respectively. VatD, which functions as ferric-hydroxamate siderophores periplasmic binding protein, was shown to participate in the ferric-vulnibactin uptake system in the absence of FatB. Furthermore, the ferric-hydroxamate
siderophore reductase IutB was observed to participate in ferric-vulnibactin reduction in the absence of VuuB. We propose that ferric-
siderophore periplasmic binding proteins and ferric-chelate reductases represent potential targets for drug discovery in the context of infectious diseases.