Abstract
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.
Highlights
The emergence and spread of pathogens harboring extended spectrum β-lactamase-like carbapenem-resistant Klebsiella pneumoniae (CR-KP), Escherichia coli, and other gram negative bacteria are major emerging threat to public health (Schwaber and Carmeli, 2008; Vatopoulos, 2008)
We have modeled K. pneumoniae infection in adult zebrafish, to study toxicity and efficacy of ASK2 isolated from Streptomyces sp
Since there are no novel antibiotics in drug development in the present century for carbapenemase producing enterobacteriaceae, the existing antibiotics have re-emerged for current medications
Summary
The emergence and spread of pathogens harboring extended spectrum β-lactamase-like carbapenem-resistant Klebsiella pneumoniae (CR-KP), Escherichia coli, and other gram negative bacteria are major emerging threat to public health (Schwaber and Carmeli, 2008; Vatopoulos, 2008). K. pneumoniae is emerged as a new MDR varieties of human pathogens that can have drastic consequences on health care worldwide (Patel et al, 2008; Struelens et al, 2010; Ulu et al, 2015). One such best example is the evolution and spread of CR-KP. The second choices of drugs are colistin, tigecycline, and fosfomycin, are more toxic than the fist-line drugs (Melano et al, 2003; Petrosillo et al, 2013)
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