Cheepurupalli Lalitha, Raman Thiagarajan, Rathore Sudarshan S, Ramakrishnan Jayapradha
Actinomycetes Bioprospecting Lab, Centre for Research in Infectious Diseases, School of Chemical and Biotechnology, SASTRA UniversityTirumalaisamudram, India.
Laboratory for Inflammation Research, Centre for Research in Infectious Diseases, School of Chemical and Biotechnology, SASTRA UniversityTirumalaisamudram, India.
Front Microbiol. 2017 Apr 12;8:614. doi: 10.3389/fmicb.2017.00614. eCollection 2017.
The emergence and spread of multi-drug resistant (MDR) especially carbapenem-resistant is a major emerging threat to public health, leading to excess in mortality rate as high as 50-86%. MDR manifests all broad mechanisms of drug resistance, hence development of new drugs to treat MDR infection has become a more relevant question in the scientific community. In the present study a potential sp. ASK2 was isolated from rhizosphere soil of medicinal plant. The multistep HPLC purification identified the active principle exhibiting antagonistic activity against MDR . 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 - zebrafish model, the infectious doses to manifest sub-clinical and clinical infection were optimized. Furthermore, the virulence of in planktonic and biofilm state was studied in zebrafish. The MTT assay of 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 sp. was potent in mitigating MDR infection.
多重耐药(MDR)尤其是耐碳青霉烯类细菌的出现和传播是对公共卫生的一个主要新出现威胁,导致死亡率高达50%-86%。多重耐药表现出所有广泛的耐药机制,因此开发治疗多重耐药感染的新药已成为科学界一个更相关的问题。在本研究中,从药用植物根际土壤中分离出一种潜在的[具体菌种名称]ASK2。多步高效液相色谱纯化鉴定出对多重耐药菌具有拮抗活性的活性成分。纯化后的化合物是一种带有脂肪族侧链分子的芳香族化合物,分子量为444.43道尔顿。傅里叶变换红外光谱显示存在羟基和羰基作为官能团。在成年斑马鱼感染模型中进一步评估了该生物活性化合物的药物诱导毒性和疗效。由于这是关于[具体菌种名称] - 斑马鱼模型的首次研究,优化了表现亚临床和临床感染的感染剂量。此外,在斑马鱼中研究了[具体菌种名称]在浮游状态和生物膜状态下的毒力。斑马鱼肝脏培养物的MTT试验表明,所提出的ASK2化合物在有效剂量下无毒性。此外,感染斑马鱼存活率的显著提高表明,来自[具体菌种名称]新菌株的ASK2化合物在减轻多重耐药菌感染方面具有效力。