Lipopolysaccharide transport protein D (Pseudomonas aeruginosa) (LptD)

Lipopolysaccharide transport protein D (LptD) is an essential outer membrane protein in Pseudomonas aeruginosa that facilitates the final stage of lipopolysaccharide (LPS) assembly. It forms a complex with the lipoprotein LptE to create a translocon that inserts LPS into the outer leaflet of the outer membrane, a process vital for maintaining the structural integrity and barrier function of Gram-negative bacteria [1][2]. Because LptD is exposed on the bacterial surface and is essential for survival, it serves as a highly specific target for novel antibiotics [3]. Murepavadin, a peptidomimetic antibiotic, specifically binds to LptD in P. aeruginosa, blocking LPS transport and resulting in rapid bactericidal activity [4]. This target is particularly significant in the context of multi-drug resistant (MDR) infections, where traditional treatments often fail [5]. However, clinical development of LptD inhibitors has faced challenges, including concerns regarding renal toxicity observed in late-stage trials [6].

Other names

OstAOrganic solvent tolerance protein AImpIncreased membrane permeability protein

Inhibition of lipopolysaccharide transport to the outer membrane, leading to membrane disruption and cell death [3][4]