Research

Life Sciences & Biotechnology

Title :

Comparative Genome-wide analysis of adaptively evolved Streptomyces mutant phenotypes and LC-MS-based profiling of bioactive metabolites produced by them

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Dharmesh Harwani, Maharaja Ganga Singh University, Bikaner, Rajasthan

Timeline Start Year :

2024

Timeline End Year :

2027

Contact info :

Details

Executive Summary :

The proposal focuses on the use of adaptive laboratory evolution to stimulate antibiotic production in a Streptomyces strain JB140, which exhibited little antimicrobial activity against bacterial pathogens. The study involved seven competition experiments, resulting in the evolution of the wild-type strain into seven unique mutant phenotypes that exhibited increased antimicrobial activity against three bacterial pathogens: Salmonella Typhi, Staphylococcus aureus, and Proteus vulgaris. These mutant phenotypes effectively inhibited the growth of the tested pathogens and improved antimicrobial responses against one clinical multidrug-resistant (MDR) uropathogenic Escherichia coli isolate. The study also revealed significant polymorphisms among the wild-type Streptomyces and its evolved mutants, providing a simple laboratory model to study the adaptive potential of evolved phenotypes in Streptomyces to induce antibiotic production. The proposed research aims to identify genetic variations and secondary bioactive metabolites produced by the seven mutant streptomycete phenotypes and their wild-type parent to understand the underlying mechanisms responsible for the adaptive evolution strategy. The proposal aims to provide possible solutions to the issues posed by MDR pathogens and provide novel and alternative antimicrobial metabolites, as the rate of discovery for antibiotics has declined since the late 1960s. The proposal aims to provide novel and alternative antimicrobial metabolites to address the serious threats posed by MDR pathogens.

Total Budget (INR):

24,46,400

Organizations involved