A new competitive strategy to unveil the antibiotic-producing Actinobacteria

Abstract

The bacterial phylum Actinobacteria encompasses microorganisms with incomparable metabolic versatility and deep resource of medicines. However, the recent decrease in the discovery rate of antibiotics warrants innovative strategies to harness actinobacterial resources for lead discovery. Indeed, microbial culturing efforts measuring the outcomes of specific genera lagged behind the detected microbial potential. Herein, we used a distinct competitive strategy that exploits competitive microbial interactions to accelerate the diversification of strain libraries producing antibiotics. This directed-evolution-based strategy shifted the diversity of Actinobacteria over the experimental time course (0-8 days) and led to the isolation of Actinobacterial strains with distinct antimicrobial spectrum against pathogens. To understand the competitive interactions over experimental time, the metagenomic community sequencing revealed that actinobacterial members from families Nocardiaceae and Cellulomonadaceae with relatively increased abundances towards end, are thus competitively advantageous. Whilst comparing the Actinobacteria retrieved in the competitive strategy to that of the routinely used isolation method, the Actinobacteria genera identified from competitive communities differed relatively in abundances as well as antimicrobial spectrum compared to actinobacterial strains retrieved in classical method. In sum, we present a strategy that influences microbial interactions to accelerate the likelihood of potential actinobacterial strains with antimicrobial potencies.