Antibiotic Resistance Crisis: From Bacterial Bioprospecting to Artificial Intelligence.

Antibiotics revolutionized medicine in the 20th century by drastically reducing mortality from bacterial infections. However, their effectiveness is threatened by the global rise of antimicrobial resistance (AMR), driven by misuse, overuse, and environmental dissemination. This review explores the historical trajectory of antibiotics, the mechanisms of bacterial resistance, and the urgent need for innovation amid a declining antibiotic development pipeline. Herein, we highlight the scientific and economic barriers that have discouraged investment by major pharmaceutical companies and examine emerging strategies to address this crisis. Key advances in microbial bioprospecting, including cultivation improvement techniques and genome mining, are discussed alongside the role of high-throughput sequencing and bioinformatics in unlocking the metabolic potential of uncultivated microorganisms. Particular emphasis is placed on the integration of artificial intelligence and machine learning to accelerate drug discovery, predict antimicrobial activity, and identify resistance genes. Additionally, we present alternative therapeutic strategies beyond traditional antibiotics, such as phage therapy, antimicrobial peptides, quorum sensing inhibitors, synthetic conjugates, and vaccine development. Together, these interdisciplinary approaches offer promising pathways to revitalize the antimicrobial pipeline and address the growing threat of antibiotic resistance.