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Sensitization of Microcin J25-Resistant Strains by a Membrane-Permeabilizing Peptide

机译:膜透化肽敏化Microcin J25耐药菌株。

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Microcin J25 (MccJ25) is a plasmid-encoded, 21-amino-acid, antibacterial peptide produced by Escherichia coli . MccJ25 inhibits RNA polymerase and the membrane respiratory chain. MccJ25 uptake into E. coli -sensitive strains is mediated by the outer membrane receptor FhuA and the inner membrane proteins TonB, ExbB, ExbD, and SbmA. This peptide is active on some E. coli , Salmonella , and Shigella species strains, while other Gram-negative bacteria, such as clinical isolates of Enterobacter cloacae , Citrobacter freundii , Klebsiella pneumoniae , Pseudomonas aeruginosa , Acinetobacter baumannii , Moraxella catarrhalis , and Salmonella enterica serovar Typhimurium, are completely resistant. In the present work, we demonstrated that the membrane-permeabilizing peptide (KFF)_(3)K made some resistant strains sensitive to MccJ25, among them S. Typhimurium, where the antibiotic inhibits in vitro cell growth and bacterial replication within macrophages. The results demonstrate that the membrane permeabilization induced by (KFF)_(3)K allows MccJ25 penetration in an FhuA and SbmA-independent manner and suggest that the combination of both peptides could be considered as a therapeutic agent against pathogenic Salmonella strains.
机译:Microcin J25(MccJ25)是由大肠杆菌生产的质粒编码的21个氨基酸的抗菌肽。 MccJ25抑制RNA聚合酶和膜呼吸链。 MccJ25被大肠杆菌敏感菌株吸收是由外膜受体FhuA和内膜蛋白TonB,ExbB,ExbD和SbmA介导的。该肽对某些大肠杆菌,沙门氏菌和志贺氏菌属菌株具有活性,而其他革兰氏阴性细菌,例如阴沟肠杆菌,弗氏柠檬酸杆菌,肺炎克雷伯菌,铜绿假单胞菌,鲍曼不动杆菌,鲍曼不动杆菌,卡他莫拉氏菌和沙门氏菌的临床分离株鼠伤寒血清型,完全耐药。在目前的工作中,我们证明了膜通透性肽(KFF)_(3)K产生了一些对MccJ25敏感的抗性菌株,其中包括鼠伤寒沙门氏菌,其中的抗生素抑制了体外细胞的生长和巨噬细胞内细菌的复制。结果表明,由(KFF)_(3)K诱导的膜通透性允许MccJ25以FhuA和SbmA独立的方式穿透,并表明这两种肽的组合可被视为抗病原性沙门氏菌菌株的治疗剂。

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