Role of Acinetobactin-Mediated Iron Acquisition Functions in the Interaction of Acinetobacter baumannii Strain ATCC 19606T with Human Lung Epithelial Cells, Galleria mellonella Caterpillars, and Mice
Role of Acinetobactin-Mediated Iron Acquisition Functions in the Interaction of Acinetobacter baumannii Strain ATCC 19606T with Human Lung Epithelial Cells, Galleria mellonella Caterpillars, and Mice
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DOI：
10.1128/iai.06279-11
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发表时间：
2012-03-01
影响因子：
3.1
通讯作者：
Actis, Luis A.
中科院分区：
文献类型：
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作者：
Gaddy, Jennifer A.;Arivett, Brock A.;Actis, Luis A.
鲍曼不动杆菌，导致免疫功能低下的患者严重感染，表达高亲和力的铁收购功能，需要在铁限制实验室条件下的增长。在这项研究中，我们确定ATCC 19606（T）型菌株与A549人肺泡上皮细胞的初始相互作用不依赖于BasD和BauA的产生，BasD和BauA分别是不动蛋白肌动蛋白生物合成和转运所需的蛋白质。相反，这些蛋白质是该菌株在上皮细胞内持续存在并导致其凋亡所必需的。使用大蜡螟幼虫进行的感染试验表明，不动肌动蛋白生物合成和转运功能的受损显著降低了ATCC 19606（T）细胞持续存在和杀死该宿主的能力，这一缺陷通过向接种物中添加无机铁得到纠正。使用小鼠脓毒症模型验证了用这些离体和体内方法获得的结果，其显示不动杆菌介导的铁获取系统的表达对于ATCC 19606（T）建立感染和杀死该脊椎动物宿主是关键的。这些观察结果表明，ATCC 19606（T）菌株的毒力取决于完全活性的不动杆菌介导系统的表达。有趣的是，这三种模型还表明，与亲本菌株和BauA突变体相比，BasD生产的受损导致中间毒力表型。这一观察结果表明，acineadipactin中间体或前体发挥毒力的作用，虽然他们的贡献，铁收购是不太相关的成熟acineadipactin。
Acinetobacter baumannii, which causes serious infections in immunocompromised patients, expresses high-affinity iron acquisition functions needed for growth under iron-limiting laboratory conditions. In this study, we determined that the initial interaction of the ATCC 19606(T) type strain with A549 human alveolar epithelial cells is independent of the production of BasD and BauA, proteins needed for acinetobactin biosynthesis and transport, respectively. In contrast, these proteins are required for this strain to persist within epithelial cells and cause their apoptotic death. Infection assays using Galleria mellonella larvae showed that impairment of acinetobactin biosynthesis and transport functions significantly reduces the ability of ATCC 19606(T) cells to persist and kill this host, a defect that was corrected by adding inorganic iron to the inocula. The results obtained with these ex vivo and in vivo approaches were validated using a mouse sepsis model, which showed that expression of the acinetobactin-mediated iron acquisition system is critical for ATCC 19606(T) to establish an infection and kill this vertebrate host. These observations demonstrate that the virulence of the ATCC 19606(T) strain depends on the expression of a fully active acinetobactin-mediated system. Interestingly, the three models also showed that impairment of BasD production results in an intermediate virulence phenotype compared to those of the parental strain and the BauA mutant. This observation suggests that acinetobactin intermediates or precursors play a virulence role, although their contribution to iron acquisition is less relevant than that of mature acinetobactin.