Transcriptional regulators: valuable targets for novel antibacterial strategies

Abstract

Antibiotics have saved millions of lives over the past decades. However, the accumulation of so many antibiotic resistance genes by some clinically relevant pathogens has begun to lead to untreatable infections worldwide. The current antibiotic resistance crisis will require greater efforts by governments and the scientific community to increase the research and development of new antibacterial drugs with new mechanisms of action. A major challenge is the identification of novel microbial targets, essential for in vivo growth or pathogenicity, whose inhibitors can overcome the currently circulating resistome of human pathogens. In this article, we focus on the potential high value of bacterial transcriptional regulators as targets for the development of new antibiotics, discussing in depth the molecular role of these regulatory proteins in bacterial physiology and pathogenesis. Recent advances in the search for novel compounds that inhibit the biological activity of relevant transcriptional regulators in pathogenic bacteria are reviewed.