Frontiers in Antimicrobial Drug Discovery: Current Approaches and Innovations

Antimicrobial drug resistance has emerged as a significant public health challenge, exacerbated by the rise of multidrug-resistant strains and the emergence of new infections. This has intensified the need for the development of novel therapeutic agents. Antibiotics, originally derived from microorganisms, are compounds that either inhibit or kill other microbes. Historically, most antibiotics used in clinical settings were produced by Actinomycetes and fungi, particularly during the golden age of antibiotic discovery (1940s to 1960s). However, progress in drug development slowed in the following decades due to challenges in cultivation techniques, including isolation difficulties, microbial overgrowth, and discrepancies between natural environments and laboratory conditions. Recently, innovative approaches, such as advancements in cultivation methods, modification of existing compounds, gene induction, exploration of animal microbiota, co-cultivations, and identification of alternative antimicrobial targets, have provided new pathways for drug discovery. Additionally, cutting-edge molecular tools like metagenomics have enabled the exploration of bioactive molecules from uncultured microbes in diverse microenvironments, potentially ushering in a new era in antibiotic development. This review examines both past and current methodologies in antimicrobial drug discovery, highlighting future perspectives for the field.