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Targeted Killing of Pseudomonas aeruginosa by Pyocin G Occurs via the Hemin Transporter Hur

机译:通过血红蛋白G通过血红素转运蛋白伯爵进行了针对性杀害假单胞菌铜绿假单胞菌

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Pseudomonas aeruginosa is a priority pathogen for the development of new antibiotics, particularly because multi-drug-resistant strains of this bacterium cause serious nosocomial infections and are the leading cause of death in cystic fibrosis patients. Pyocins, bacteriocins of P. aeruginosa, are potent and diverse protein antibiotics that are deployed during bacterial competition. Pyocins are produced by more than 90% of P. aeruginosa strains and may have utility as last resort antibiotics against this bacterium. In this study, we explore the antimicrobial activity of a newly discovered pyocin called pyocin G (PyoG). We demonstrate that PyoG has broad killing activity against a collection of clinical P. aeruginosa isolates and is active in a Galleria mellonella infection model. We go on to identify cell envelope proteins that are necessary for the import of PyoG and its killing activity. PyoG recognizes bacterial cells by binding to Hur, an outer-membrane TonB-dependent transporter. Both pyocin and Hur interact with TonB1, which in complex with ExbB-ExbD links the proton motive force generated across the inner membrane with energy-dependent pyocin translocation across the outer membrane. Inner-membrane translocation of PyoG is dependent on the conserved innermembrane AAA + ATPase/protease, FtsH. We also report a functional exploration of the PyoG receptor. We demonstrate that Hur can bind to hemin in vitro and that this interaction is blocked by PyoG, confirming the role of Hur in hemin acquisition. (C) 2020 The Authors. Published by Elsevier Ltd.
机译:铜绿假单胞菌是一种优先发病原,用于开发新的抗生素,特别是因为这种细菌的多毒性抗药性导致严重的医院感染,并且是囊性纤维化患者死亡的主要原因。 P.铜绿假单胞菌的菌丝,铜菌,是在细菌竞争期间部署的有效和多样化的蛋白质抗生素。豆素由90%以上的P.铜绿假单胞菌菌株产生,并且可能与对该细菌的最后起诉抗生素有用。在这项研究中,我们探讨了新发现的豆荚的抗微生物活性,称为斑霉素G(臀)。我们展示臀对针对临床P.铜绿假单胞菌的集合具有广泛的杀戮活动,并在Galleria Mellonella感染模型中活跃。我们继续识别臀部导入所必需的细胞包膜蛋白及其杀戮活动。臀通过结合Hur,外膜Tonb依赖性转运蛋白来识别细菌细胞。豆蛋白和HUN都与TONB1相互作用,该TONB1与EXBB-EXBD将在内膜上产生的质子动力联系在外膜上的能量依赖性曲霉素易位。臀的内膜易位依赖于保守的innermbrane AAA + ATP酶/蛋白酶,FTSH。我们还报告了对臀受体的功能探索。我们证明HUR可以在体外与血红素结合,并且这种相互作用被臀阻断,确认HUR在血红素习得中的作用。 (c)2020作者。 elsevier有限公司出版

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