Undecaprenyl pyrophosphate and undecaprenyl pyrophosphate phosphatase (UPP/UPP phosphatase)

Undecaprenyl pyrophosphate (UPP), also known as C55-isoprenyl pyrophosphate or bactoprenol pyrophosphate, is an essential lipid carrier in bacteria that transports peptidoglycan precursors across the cytoplasmic membrane (Manat et al., 2014, PubMed: 25100633). After delivering the precursor to the cell wall assembly site, UPP must be dephosphorylated by undecaprenyl pyrophosphate phosphatases, such as UppP (BacA), to regenerate undecaprenyl phosphate (UP) for further transport cycles (El Ghachi et al., 2004, PubMed: 15251211). This dephosphorylation step is a critical bottleneck in bacterial cell wall synthesis. The antibiotic bacitracin targets this process by forming a complex with UPP in the presence of divalent metal ions, which prevents the phosphatase from acting on the substrate (Stone and Strominger, 1971, PubMed: 4328831). This sequestration leads to the depletion of the available lipid carrier pool, effectively halting cell wall production and causing bacterial cell death. Because this lipid-mediated transport system is unique to prokaryotes, it serves as a specific target for antimicrobial therapy, although the systemic toxicity of bacitracin limits its clinical use to topical applications (StatPearls, 2023).

Other names

C55-isoprenyl pyrophosphateBactoprenol pyrophosphateUndecaprenyl-diphosphateUppPBacAUndecaprenyl pyrophosphate phosphatase

Bacitracin binds to undecaprenyl pyrophosphate in a metal-dependent manner, preventing its dephosphorylation by undecaprenyl pyrophosphate phosphatase and thereby blocking the recycling of the lipid carrier essential for cell wall synthesis.