A multi-step analysis including GCI reveals novel insight into LPS translocation

Antibiotic resistance is one of the key health challenges of the future. In a new study, researchers have carried out a multi-step analysis to deliver insights into translocation of the hydrophobic and hydrophilic portions of the large lipopolysaccharide molecules through the outer membrane of Neisseria gonorrhoeae. This article summarises their work.

Neisseria gonorrhoeae (Ng) is a type of Gram-negative bacteria, which are especially problematic as they are well-shielded from their environment by an outer membrane (OM) that establishes a tight barrier for several antibiotics due to the high density of lipopolysaccharides (LPS) in the outer leaflet of the membrane. The last step of LPS insertion via the Lpt pathway is mediated by the LptD/E protein complex. Detailed insights into the architecture of LptDE transporter complexes have been derived from X-ray crystallography. However, no structure of a laterally open LptD transporter, a transient state that occurs during LPS release, is available to date.

A new multi-step analysis has delivered novel insights into the mechanism of LPS insertion, providing a structural framework for the development of antibiotics targeting LptD and describing a highly rigid chaperone scaffold to enable structural biology of challenging…