The Acinetobacter baumannii entA gene located outside the acinetobactin cluster is critical for siderophore production, iron acquisition and virulence.
The Acinetobacter baumannii entA gene located outside the acinetobactin cluster is critical for siderophore production, iron acquisition and virulence.
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DOI：
10.1371/journal.pone.0036493
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Actis LA
中科院分区：
文献类型：
--
作者：
Penwell WF;Arivett BA;Actis LA
鲍氏不动杆菌会在受损患者中引起严重感染，这些患者提供了一个控制细菌生长的铁限制环境。该病原体通过表达高亲和力铁获取系统（包括由铁载体腺泡肌动蛋白介导的系统）来响应这种限制。基因克隆、功能测定和生化试验表明，A.鲍曼不动杆菌基因组含有单一功能拷贝的entA直系同源物。该基因对于不动肌动蛋白前体2，3-二羟基苯甲酸（DHBA）的生物合成是必需的，位于不动肌动蛋白基因簇的外部，否则该基因簇含有不动肌动蛋白生物合成、输出和运输所需的所有基因。计算机模拟分析和遗传互补测试表明，entA位于entB直系同源物旁边，其编码含有异分支酶裂解酶结构域的推定蛋白质，该结构域是从异氯酸生物合成DHBA所需的，但缺乏芳基载体蛋白结构域，该结构域是拴系活化的DHBA和完成铁载体生物合成所需的。因此，basF，它位于acinegrin肌动蛋白基因簇，是唯一的全功能entB直系同源物存在于ATCC 19606 T。这两种EntB直向同源物之间氨基酸长度和序列的差异以及在不同A.鲍曼不动杆菌分离株表明它们是通过水平转移从不同来源获得的。有趣的是，AYE菌株被证明是一种天然的entA突变体，能够通过未表征的铁载体介导的系统获得铁，这一观察结果强调了不同A.鲍曼不动杆菌分离物使用不同的系统获得铁。最后，使用体内和离体模型的实验感染证明了DHBA和无动肌动蛋白中间体在ATCC 19606 T细胞的毒力中的作用，尽管与用产生和使用完全成熟的无动肌动蛋白以获得铁的细菌获得的应答相比在较小程度上。
Acinetobacter baumannii causes severe infections in compromised patients, who present an iron-limited environment that controls bacterial growth. This pathogen has responded to this restriction by expressing high-affinity iron acquisition systems including that mediated by the siderophore acinetobactin. Gene cloning, functional assays and biochemical tests showed that the A. baumannii genome contains a single functional copy of an entA ortholog. This gene, which is essential for the biosynthesis of the acinetobactin precursor 2,3-dihydroxybenzoic acid (DHBA), locates outside of the acinetobactin gene cluster, which otherwise harbors all genes needed for acinetobactin biosynthesis, export and transport. In silico analyses and genetic complementation tests showed that entA locates next to an entB ortholog, which codes for a putative protein that contains the isochorismatase lyase domain, which is needed for DHBA biosynthesis from isochorismic acid, but lacks the aryl carrier protein domain, which is needed for tethering activated DHBA and completion of siderophore biosynthesis. Thus, basF, which locates within the acinetobactin gene cluster, is the only fully functional entB ortholog present in ATCC 19606T. The differences in amino acid length and sequences between these two EntB orthologs and the differences in the genetic context within which the entA and entB genes are found in different A. baumannii isolates indicate that they were acquired from different sources by horizontal transfer. Interestingly, the AYE strain proved to be a natural entA mutant capable of acquiring iron via an uncharacterized siderophore-mediated system, an observation that underlines the ability of different A. baumannii isolates to acquire iron using different systems. Finally, experimental infections using in vivo and ex vivo models demonstrate the role of DHBA and acinetobactin intermediates in the virulence of the ATCC 19606T cells, although to a lesser extent when compared to the responses obtained with bacteria producing and using fully matured acinetobactin to acquire iron.
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