From Soil to Shelf: Teixobactin at TenMechanism, SAR, and the Road to Clinical Application

Isolated from the previously unculturable soil bacterium Eleftheria terrae using the innovative iChip technology, teixobactin initially showed the remarkable ability to kill pathogens without apparent development of resistance. Over the past decade, intensive research has unraveled a complex mode of action: teixobactin dual-targets the essential cell wall precursors Lipid II and Lipid III, then triggers a cascade of self-assembly into amyloid-like fibrils on bacterial membranes, sequestering these precursors and lysing the cell.

Commemorating its 10th anniversary, this review provides a comprehensive analysis of teixobactin’s journey. We examine key structure–activity relationships (SAR) derived from the synthesis of numerous analogs that identified critical residues and moieties required for activity and led to promising derivative compounds. At the same time, the road from soil to clinic has been marked by challenges.