Dual targeting of cell wall precursors by teixobactin leads to cell lysis

Tomoyuki Homma, Austin Nuxoll, Autumn Brown Gandt, Patrick Ebner, Ina Engels, Tanja Schneider, Friedrich Götz, Kim Lewis, Brian P. Conlon

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Teixobactin represents the first member of a newly discovered class of antibiotics that act through inhibition of cell wall synthesis. Teixobactin binds multiple bactoprenol-coupled cell wall precursors, inhibiting both peptidoglycan and teichoic acid synthesis. Here, we show that the impressive bactericidal activity of teixobactin is due to the synergistic inhibition of both targets, resulting in cell wall damage, delocalization of autolysins, and subsequent cell lysis. We also find that teixobactin does not bind mature peptidoglycan, further increasing its activity at high cell densities and against vancomycin-intermediate Staphylococcus aureus (VISA) isolates with thickened peptidoglycan layers. These findings add to the attractiveness of teixobactin as a potential therapeutic agent for the treatment of infection caused by antibiotic-resistant Gram-positive pathogens.

Original languageEnglish (US)
Pages (from-to)6510-6517
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number11
DOIs
StatePublished - Nov 2016

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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