Hijacking the Heme Acquisition System of Pseudomonas aeruginosa for the Delivery of Phthalocyanine as an Antimicrobial
Hijacking the Heme Acquisition System of Pseudomonas aeruginosa for the Delivery of Phthalocyanine as an Antimicrobial
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DOI：
10.1021/acschembio.9b00373
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发表时间：
2019-07-01
影响因子：
4
通讯作者：
Shoji, Osami
中科院分区：
文献类型：
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作者：
Shisaka, Yuma;Iwai, Yusuke;Shoji, Osami
为了在宿主缺乏铁的环境中生存，病原菌设计了各种狡猾的策略，例如进化复杂的血红素运输系统来掠夺细胞外血红素。然而，血红素转运系统作为抗微生物靶点的潜力还没有被探索。在此，我们开发了一种策略，通过利用铜绿假单胞菌的细胞外血红素获取系统蛋白A（HasA）提供抗菌剂。我们证明，类似于血红素摄取，HasA可以通过HasA与其外膜受体HasR的相互作用，特异性地将抗菌剂酞菁镓（GaPc）运输到铜绿假单胞菌的细胞内空间。HasA使得水不溶性GaPc能够被铜绿假单胞菌错误地获得，从而允许其通过用近红外（NIR）光照射而灭菌（>99.99%），而不管抗生素抗性。我们的研究结果证实，细菌血红素摄取通过蛋白质蛋白质识别是一个有吸引力的目标抗菌剂，使具体和有效的杀菌。
To survive in the iron-devoid environment of their host, pathogenic bacteria have devised multifarious cunning tactics such as evolving intricate heme transport systems to pirate extracellular heme. Yet, the potential of heme transport systems as antimicrobial targets has not been explored. Herein we developed a strategy to deliver antimicrobials by exploiting the extracellular heme acquisition system protein A (HasA) of Pseudomonas aeruginosa. We demonstrated that, analogous to heme uptake, HasA can specifically traffic an antimicrobial, gallium phthalocyanine (GaPc), into the intracellular space of P. aeruginosa via the interaction of HasA with its outer membrane receptor HasR. HasA enables water-insoluble GaPc to be mistakenly acquired by P. aeruginosa, permitting its sterilization (>99.99%) by irradiation with near-infrared (NIR) light, irrespective of antibiotic resistance. Our findings substantiate that bacterial heme uptake via protein protein recognition is an attractive target for antimicrobials, enabling specific and effective sterilization.