AvH Benchfee

Exploration of Novel Bioactive Secondary Metabolites of Streptomyces spp. isolated from soil of Mountains regions of Nepal

16.08.2018 bis 15.11.2018

Streptomyces is the largest antibiotics producing genus that produces over two-third of the clinically useful antibiotics in addition to other useful drugs such as anticancer and antifungal medicines. Research in antibiotics is un-ending science as the existing antibiotics may not work in future due to evolution of antibiotic resistant varieties of human bacterial pathogen. Many existing antibiotics are not effective especially for Streptococcus pneumoniae, MRSA (Methicillin resistant Staphylococcus aureus), Mycobacterium tuberculosis and many more. More that 70% of pathogenic bacteria were estimated to be resistant to at least one of the currently available antibiotics. Therefore, the search of new sources and several new generations of antibiotics are crucial for human health care systems. Nepal’s high altitude regions have extreme environment-high UV, drought and cold. The region is scientifically unexplored in the field of microbial diversity and their natural product chemistry. Therefore, there is a high chance of obtaining the novel species of Streptomyces and new generation of novel antimicrobial compounds from this research project. More than one hundred Streptomyces strains have been isolated by using serial dilution method from the soil samples of various places of western and central region of Nepal in the laboratory of Department of Biodiversity and Natural Product, Center for Natural and Applied Sciences, Kathmandu, Nepal. ISP2 and ISP4 culture media were used to isolate the bacterial strains. Preliminary biological activity screening assay showed that a total of twenty strains were active against Staphylococcus aureus, Bacillus subtilis and Escherichia coli. Two strains showed very strong toxic activity against Brine shrimp larvae when compared to commercial standard berberine chloride. During the present research project, one strong Brine shrimp toxicity showing and one strong antimicrobial activity showing bacterial strains will be subjected to further work to isolate and characterize active natural compounds. The work will be conducted in the laboratory of Prof. Harald Gross, at Department of Pharmaceutical Biology, University of Tübingen, Germany. A well grown broth culture (9L) of active strains will be extracted with ethyl acetate. Various chromatography techniques will be used to separate active fractions. The molecular structure of the purified active fractions will be determined by analyzing data obtained from various spectroscopic experiments and chemical derivatization. And the finally, the biological activity of the active compounds will be determined quantitatively and compared with commercial standard drugs. At last, chemical elicitation based OSMAC techniques will be applied to perform comparative study in the biosynthetic natural products variation in the tested Streptomyces strains.