Department of Microbiology and Infection Control, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Department of Physical Chemistry, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Mar Drugs. 2021 Dec 17;19(12):710. doi: 10.3390/md19120710.
is a Gram-negative pathogenic bacterium that causes serious infections in humans and requires iron for growth. A clinical isolate, . M2799, secretes a catecholate siderophore, vulnibactin, that captures ferric ions from the environment. In the ferric-utilization system in . M2799, an isochorismate synthase (ICS) and an outer membrane receptor, VuuA, are required under low-iron conditions, but alternative proteins FatB and VuuB can function as a periplasmic-binding protein and a ferric-chelate reductase, respectively. The vulnibactin-export system is assembled from TolCV1 and several RND proteins, including VV1_1681. In heme acquisition, HupA and HvtA serve as specific outer membrane receptors and HupB is a sole periplasmic-binding protein, unlike FatB in the ferric-vulnibactin utilization system. We propose that ferric-siderophore periplasmic-binding proteins and ferric-chelate reductases are potential targets for drug discovery in infectious diseases.
是一种革兰氏阴性病原菌,可导致人类严重感染,其生长需要铁。临床分离株. M2799 分泌一种儿茶酚载体铁载体,即 Vulnibactin,可从环境中捕获三价铁离子。在. M2799 的铁利用系统中,异分支酸合酶 (ICS) 和外膜受体 VuuA 在低铁条件下是必需的,但替代蛋白 FatB 和 VuuB 可以分别作为周质结合蛋白和三价铁螯合物还原酶发挥作用。Vulnibactin 外排系统由 TolCV1 和几个 RND 蛋白组成,包括 VV1_1681。在血红素获取中,HupA 和 HvtA 作为特定的外膜受体,HupB 是唯一的周质结合蛋白,与铁载体 Vulnibactin 利用系统中的 FatB 不同。我们提出,铁载体周质结合蛋白和铁螯合物还原酶是传染病药物发现的潜在靶点。