LPS-assembly protein LptD (LptD)

LPS-assembly protein LptD is an essential integral outer membrane protein in the Gram-negative pathogen Pseudomonas aeruginosa [1, 6]. It forms a translocon complex with the lipoprotein LptE, which is responsible for the final stage of transporting lipopolysaccharide (LPS) molecules from the periplasm to the outer leaflet of the outer membrane [1, 8]. This process is vital for maintaining the structural integrity and barrier function of the bacterial cell envelope, which protects the organism from environmental stressors and antibiotics [10, 16]. Due to its critical role in bacterial survival and its location on the cell surface, LptD is a prominent target for the development of novel antibiotics, such as the macrocyclic peptidomimetic Murepavadin [1, 3]. These therapeutic agents typically bind to the periplasmic domain of LptD, effectively blocking LPS assembly and leading to rapid bacterial cell death [2, 4]. While promising, the clinical application of LptD inhibitors has encountered challenges, including concerns regarding nephrotoxicity and the emergence of resistance through specific mutations in the lptD gene [1, 10, 19].

Other names

impostAOrganic solvent tolerance protein ALipopolysaccharide transport protein DPA0595

Inhibition of lipopolysaccharide (LPS) transport to the outer membrane by binding to the LptD protein, leading to outer membrane disruption and bacterial cell death.