Bioactive Molecule from Streptomyces sp. Mitigates MDR Klebsiella pneumoniae in Zebrafish Infection Model.
Bioactive Molecule from Streptomyces sp. Mitigates MDR Klebsiella pneumoniae in Zebrafish Infection Model.
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DOI：
10.3389/fmicb.2017.00614
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发表时间：
2017
影响因子：
5.2
通讯作者：
Ramakrishnan J
中科院分区：
文献类型：
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作者：
Cheepurupalli L;Raman T;Rathore SS;Ramakrishnan J
多重耐药（MDR）尤其是耐碳青霉烯类肺炎克雷伯菌的出现和传播是对公共健康的主要威胁，导致死亡率高达 50-86%。耐多药肺炎克雷伯菌表现出所有广泛的耐药机制，因此开发治疗耐多药肺炎克雷伯菌感染的新药已成为科学界更相关的问题。在本研究中，潜在的链霉菌属。 ASK2是从药用植物根际土壤中分离得到的。多步 HPLC 纯化鉴定出对 MDR 肺炎克雷伯菌具有拮抗活性的活性成分。发现纯化的化合物是具有脂肪族侧链分子的芳香族化合物，分子量为444.43Da。 FT-IR 显示存在 OH 和 C=O 作为官能团。进一步评估了该生物活性化合物在成年斑马鱼感染模型中的药物诱导毒性和功效。由于这是首次针对肺炎克雷伯菌-斑马鱼模型的研究，因此对表现亚临床和临床感染的感染剂量进行了优化。此外，在斑马鱼中研究了浮游和生物膜状态下肺炎克雷伯菌的毒力。斑马鱼肝脏离体培养物的 MTT 测定揭示了所提出的 ASK2 化合物在有效剂量下的无毒性质。此外，受感染斑马鱼的存活率显着增加，表明来自链霉菌新菌株的 ASK2 化合物。能够有效减轻耐多药肺炎克雷伯菌感染。
The emergence and spread of multi-drug resistant (MDR) especially carbapenem-resistant Klebsiella pneumoniae is a major emerging threat to public health, leading to excess in mortality rate as high as 50–86%. MDR K. pneumoniae manifests all broad mechanisms of drug resistance, hence development of new drugs to treat MDR K. pneumoniae infection has become a more relevant question in the scientific community. In the present study a potential Streptomyces sp. ASK2 was isolated from rhizosphere soil of medicinal plant. The multistep HPLC purification identified the active principle exhibiting antagonistic activity against MDR K. pneumoniae. The purified compound was found to be an aromatic compound with aliphatic side chain molecule having a molecular weight of 444.43 Da. FT-IR showed the presence of OH and C=O as functional groups. The bioactive compound was further evaluated for drug induced toxicity and efficacy in adult zebrafish infection model. As this is the first study on K. pneumoniae – zebrafish model, the infectious doses to manifest sub-clinical and clinical infection were optimized. Furthermore, the virulence of K. pneumoniae in planktonic and biofilm state was studied in zebrafish. The MTT assay of ex vivo culture of zebrafish liver reveals non-toxic nature of the proposed ASK2 compound at an effective dose. Moreover, significant increase in survival rate of infected zebrafish suggests that ASK2 compound from a new strain of Streptomyces sp. was potent in mitigating MDR K. pneumoniae infection.