Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2016

Teixobactin - a new antibiotic that kills by dual target inhibition (#13)

Brian Conlon 1
  1. Northeastern University, Boston, MA, United States

Teixobactin represents the first member of a new class of antibiotics. We previously showed that teixobactin kills a number of gram-positive bacteria and causes extensive cell lysis. We have yet to identify a mutant resistant to teixobactin. The mechanism of action of teixobactin is unique in that it inhibits peptidoglycan biosynthesis and teichoic acid biosynthesis. We find that the inhibition of these dual targets results in a synergistic effect that yields the impressive cidal and lytic activities of the antibiotic in Staphylococcus aureus. Inhibition of teichoic acid biosynthesis leads to a delocalization of the major autolysin Atl, while inhibition of peptidoglycan biosynthesis causes further cell wall damage and results in cell lysis. We also show that teixobactin fails to bind mature cell wall peptidoglycan, explaining it’s impressive activity against vancomycin intermediate resistant strains of S. aureus.