Secondary metabolite profile of Streptomyces spp. changes when grown with the sub-lethal concentration of silver nanoparticles: possible implication in novel compound discovery.

The decline of new antibiotics and the emergence of multidrug resistance in pathogens necessitates a revisit of strategies used for lead compound discovery. This study proposes to induce the production of bioactive compounds with sub-lethal concentrations of silver nanoparticles (Ag-NPs). A total of Forty-two Actinobacteria isolates from four Saudi soil samples were grown with and without sub-lethal concentration of Ag-NPs (50 µg ml^-1). The spent broth grown with Ag-NPs, or without Ag-NPs were screened for antimicrobial activity against four bacteria. Interestingly, out of 42 strains, broths of three strains grown with sub-lethal concentration of Ag-NPs exhibit antimicrobial activity against Staphylococcus aureus and Micrococcus luteus. Among these, two strains S4-4 and S4-21 identified as Streptomyces labedae and Streptomyces tirandamycinicus based on 16S rRNA gene sequence were selected for detailed study. The change in the secondary metabolites profile in the presence of Ag-NPs was evaluated using GC-MS and LC-MS analyses. Butanol extracts of spent broth grown with Ag-NPs exhibit strong antimicrobial activity against M. luteus and S. aureus. While the extracts of the controls with the same concentration of Ag-NPs do not show any activity. GC-analysis revealed a clear change in the secondary metabolite profile when grown with Ag-NPs. Similarly, the LC-MS patterns also differ significantly. Results of this study, strongly suggest that sub-lethal concentrations of Ag-NPs influence the production of secondary metabolites by Streptomyces. Besides, LC-MS results identified possible secondary metabolites, associated with oxidative stress and antimicrobial activities. This strategy can be used to possibly induce cryptic biosynthetic gene clusters for the discovery of new lead compounds.