A new antibiotic traps lipopolysaccharide in its intermembrane transporter

Abstract Gram-negative bacteria are extraordinarily difficult to kill because their cytoplasmic membrane is surrounded by an outer membrane that blocks the entry of most antibiotics. The impenetrable nature of the outer membrane is due to the presence of a large, amphipathic glycolipid called lipopolysaccharide (LPS) in its outer leaflet 1 . Assembly of the outer membrane requires transport of LPS across a protein bridge that spans from the cytoplasmic membrane to the cell surface. Maintaining outer membrane integrity is essential for bacterial cell viability, and its disruption can increase susceptibility to other antibiotics 2–6 . Thus, inhibitors of the seven lipopolysaccharide transport (Lpt) proteins that…

• HH
  Howard Hughes Medical Institute
• NI
  National Institutes of Health

  Awards: U19 AI158028, AI153358