Studies on the heme uptake system of a human pathogenic vibrio

创伤弧菌是引起败血症或伤口感染的一种机会性病原体，它能从多种血红素蛋白中获得铁。该过程涉及血红素蛋白被外切蛋白酶消化以使原血红素游离。在本研究中，我们研究了这种人类致病性弧菌的血红素摄取系统。在许多人类病原体中，已知血红素通过特异性外膜受体固定在细菌细胞表面。因此，我们最初测试了血红素受体的存在。发现细菌在血红素存在下表达新的外膜蛋白。但这些蛋白均不能与血红素结合，说明创伤弧菌对血红素的利用不依赖于外膜受体.我们分离并鉴定了一个血红素利用突变体。一个突变体的处理与化学诱变剂被证明是无法使用原血红素或血红素蛋白质，但在培养基中增加补充铁铁载体，如铁vulnibactin。这一发现表明，创伤弧菌具有专门的血红素摄取系统。3.创伤弧菌被发现利用合成的血红素化合物（Fe-TPPS），以及天然的（血红素）。利用任一血红素化合物的能力被过量的Cu-TPPS（血红素化合物的类似物）竞争性地消除。因此，创伤弧菌的血红素摄取系统可能不是特异性的血红素摄取系统。

Vibrio vulnificus, an opprtunistic human pathogen causing septicemia or wound infection, can obtain iron from a variety of heme proteins. This process involves the digestion of heme proteins by an exoprotease to leberate protoheme. In the present study, we investigated the protoheme uptake system of this human pathogenic vibrio.1. In many human pathogens, protoheme is known to be fixed on the bacterial cell surface by the specific outer membrane receptor. Thus, we initially tested the presence of the protoheme receptor. The bacterium was found to express novel outer membrane proteins in the presence of protoheme. However, any of these proteins could not bind to protoheme, indicating V.vulnificus utilizes protoheme independent of the outer membrane receptor.2. We isolated and characterized a mutant for protoheme utilization. One mutant isolated by treatment with a chemical mutagen was shown to be unable to use either protoheme or heme proteins, but multiplied in a medium supplemented with an iron-siderophore, uch as iron-vulnibactin. This finding demonstrates that V.vulnificus has the specialized protoheme uptake system.3.V.vulnificus was found to utilize a synthetic heme compound (Fe-TPPS), as well as natural one(protoheme). The ability to utilize either heme compounds was competitively abolished by an excess amount of Cu-TPPS,an analog of the heme compound. Therefore, the protoheme uptake system in V.vulnificus may be not specific protoheme.