Novel antibiotic discovery and the antibiotic resistome

The success of antibiotics in the therapy of infectious diseases is overshadowed by almost inevitable emergence and dissemination of resistances toward these agents, which results in higher morbidity and mortality rates and increased costs. New strategies are now needed to both limit the risk of resistance and to discover new drugs that are efficacious.

This review investigates the resistance problems through evolutionary lenses to better understand and potentially design improved therapeutics for infectious diseases. Furthermore, it gives an overview of the evolutionary history of antibiotic resistance genes and antibiotic biosynthesis genes/clusters, the structures of natural resistomes, and the regulatory roles of antibiotics. The author utilized ScienceDirect, PubMed, Web of Science and Google Scholar using the article's keywords and their combinations to retrieve the most relevant and up-to-date information.

Antibiotics and their corresponding resistances are ancient phenomena with their evolutionary timescales measured over a vast amount of time. Humans have also benefitted from access to, and the use of, a diverse range of antibiotics for many years also but have disrupted the balance by producing and using enormous amounts of antibiotics that have not existed before in natural ecosystems. This selective pressure has resulted in a tremendous expansion of resistomes. Future antibiotic discovery and development may need to pivot from exploiting extant antibiotic scaffolds and bacterial targets to reduce the risk of the rapid emergence of resistance from existing resistomes.