Lipopolysaccharide transport protein D (LptD) (LptD)

Lipopolysaccharide transport protein D (LptD) is an essential 26-stranded beta-barrel outer membrane protein in Pseudomonas aeruginosa that forms a complex with LptE to facilitate the final step of lipopolysaccharide (LPS) translocation to the cell surface (UniProt Q9I0F3; Srinivas et al., 2010). LPS is a fundamental component of the Gram-negative outer membrane, acting as a protective barrier against environmental stressors and antibiotics (Sperandeo et al., 2008). The LptD-LPS complex is a validated therapeutic target; for instance, the macrocyclic peptidomimetic Murepavadin (POL7080) specifically binds to LptD in P. aeruginosa, blocking the transport of LPS (Srinivas et al., 2010; Werth, 2015). This inhibition results in the accumulation of LPS in the periplasm, leading to membrane instability and rapid bactericidal activity (Botos et al., 2016). Targeting this specific machinery is a promising strategy for addressing multi-drug resistant (MDR) P. aeruginosa infections, although clinical trials have highlighted concerns regarding renal safety (ClinicalTrials.gov, 2019).

Other names

OstAOrganic solvent tolerance protein ALPS transport protein DLptD-LptE complexPA0595

Inhibition of the LptD-mediated transport of lipopolysaccharides to the outer membrane