Lipid A export ATP-binding cassette transporter MsbA (MsbA)

MsbA is an essential ATP-binding cassette (ABC) transporter located in the inner membrane of Gram-negative bacteria, including pathogens like Escherichia coli and Pseudomonas aeruginosa [UniProt: P0ABK5]. It functions as a flippase, using ATP hydrolysis to move Lipid A—the core component of lipopolysaccharide (LPS)—from the inner to the outer leaflet of the cytoplasmic membrane [PubMed: 29364876]. This translocation is a critical bottleneck in the assembly of the bacterial outer membrane, which provides a formidable barrier against many antibiotics. Due to its essentiality and the absence of a human homolog, MsbA is a validated target for novel antimicrobial agents [PubMed: 30045871]. Small molecule inhibitors like G007L and G907 bind to the transmembrane domain, trapping the transporter in an inward-facing conformation and preventing Lipid A export, which ultimately leads to bacterial cell death [PubMed: 29364876].

Other names

Lipid A flippaseABC transporter MsbALipid A export proteinMultidrug resistance protein homolog MsbA

Inhibitors bind to the transmembrane domain of MsbA, stabilizing an inward-facing, "apo" conformation that prevents the binding and flipping of Lipid A, thereby disrupting lipopolysaccharide transport and outer membrane integrity [PubMed: 29364876, 30045871].