Two broadly conserved families of polyprenyl-phosphate transporters

Peptidoglycan and almost all surface glycopolymers in bacteria are built in the cytoplasm on the lipid carrier undecaprenyl phosphate (UndP)(1-4). These UndP-linked precursors are transported across the membrane and polymerized or directly transferred to surface polymers, lipids or proteins. UndP is then flipped to regenerate the pool of cytoplasmic-facing UndP. The identity of the flippase that catalyses transport has remained unknown. Here, using the antibiotic amphomycin that targets UndP(5-7), we identified two broadly conserved protein families that affect UndP recycling. One (UptA) is a member of the DedA superfamily(8); the other (PopT) contains the domain DUF368. Genetic, cytological and syntenic analyses indicate that these proteins are UndP transporters. Notably, homologues from Gram-positive and Gram-negative bacteria promote UndP transport in Bacillus subtilis, indicating that recycling activity is broadly conserved among family members. Inhibitors of these flippases could potentiate the activity of antibiotics targeting the cell envelope.

Automated summary

Peptidoglycan and surface glycopolymers in bacteria are built on the lipid carrier UndP in the cytoplasm, and the identity of the flippase responsible for UndP transport has remained unknown. Using the antibiotic amphomycin, two protein families (UptA and PopT) that affect UndP recycling were identified. These proteins are widely conserved among bacteria and inhibitors of these flippases could enhance the activity of antibiotics targeting the cell envelope.