Details

Autor(en) / Beteiligte

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

Titel

Dual Targeting of Cell Wall Precursors by Teixobactin Leads to Cell Lysis

Ist Teil von

• Antimicrobial agents and chemotherapy, 2016-11, Vol.60 (11), p.6510-6517

Ort / Verlag

United States: American Society for Microbiology

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.