Clearing an ESKAPE Pathogen in a Model Organism; A Polypyridyl Ruthenium(II) Complex Theranostic that Treats a Resistant Acinetobacter baumannii Infection in Galleria mellonella
Clearing an ESKAPE Pathogen in a Model Organism; A Polypyridyl Ruthenium(II) Complex Theranostic that Treats a Resistant Acinetobacter baumannii Infection in Galleria mellonella
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清除模型生物中的 ESKAPE 病原体；
DOI：
10.1002/chem.202203555
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Smitten K
中科院分区：
文献类型：
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作者：
Smitten K
在以前的研究中，我们已经描述了基于四吡啶吩那嗪、tpphz桥接配体的发光双核钌（II）配合物对大肠杆菌和粪肠球菌致病性菌株的治疗作用。本文报道了该复合物对革兰氏阴性ESKAPE病原菌鲍曼动杆菌（AB12、AB16、AB184和AB210）和铜绿假单胞菌（PA2017、pa007imp和pa004crcn）的抗菌活性。估计的最低抑菌浓度和最低杀菌浓度表明，该复合物对真主安拉具有有效的活性。鲍曼菌株，在葡萄糖定义的最低培养基和标准营养丰富的Mueller‐Hinton‐II中。虽然p的活性较低。在碳青霉烯耐药菌株中观察到中高效力的金黄色葡萄球菌。光学显微镜显示该化合物被a迅速内化。baumannii。由于先前的报告显示，该复合物在80mg /kg浓度下对大麦草过敏原没有毒性，因此在该模型中探索了清除致病性感染的能力。各细菌对幼虫的致病浓度AB184≥105，PA2017≥103CFU/mL。人们发现单次服用这种化合物就完全清除了一种病原体。所有治疗的鲍曼杆菌感染。在96小时内剥落。独特的是，在这些条件下，由于该复合物的成像特性，清除了g的血淋巴内的细菌。通过光学显微镜和透射电子显微镜可以直接观察到mellonellae。
In previous studies we have described the therapeutic action of luminescent dinuclear ruthenium(II) complexes based on the tetrapyridylphenazine, tpphz, bridging ligand on pathogenic strains ofEscherichia coliandEnterococcus faecalis. Herein, the antimicrobial activity of the complex against pernicious Gram‐negative ESKAPE pathogenic strains ofAcinetobacter baumannii(AB12, AB16, AB184 and AB210) andPseudomonas aeruginosa(PA2017, PA_ 007_ IMP and PA_ 004_ CRCN) are reported. Estimated minimum inhibitory concentrations and minimum bactericidal concentrations for the complexes revealed the complex shows potent activity against allA. baumanniistrains, in both glucose defined minimal media and standard nutrient rich Mueller‐Hinton‐II. Although the activity was lower inP. aureginosa, a moderately high potency was observed and retained in carbapenem‐resistant strains. Optical microscopy showed that the compound is rapidly internalized byA. baumannii. As previous reports had revealed the complex exhibited no toxicity inGalleria Mellonellaup to concentrations of 80 mg/kg, the ability to clear pathogenic infection within this model was explored. The pathogenic concentrations to the larvae for each bacterium were determined to be≥105for AB184 and≥103CFU/mL for PA2017. It was found a single dose of the compound totally cleared a pathogenicA. baumanniiinfection from all treatedG. mellonellawithin 96 h. Uniquely, in these conditions thanks to the imaging properties of the complex the clearance of the bacteria within the hemolymph ofG. mellonellacould be directly visualized through both optical and transmission electron microscopy.