Two broadly conserved families of polyprenyl-phosphate transporters
- 30 November 2022
- journal article
- research article
- Published by Springer Nature in Nature
- Vol. 613 (7945) , 729-734
Abstract
Peptidoglycan and almost all surface glycopolymers in bacteria are built in the cytoplasm on the lipid carrier undecaprenyl phosphate (UndP)1,2,3,4. 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 UndP5,6,7, we identified two broadly conserved protein families that affect UndP recycling. One (UptA) is a member of the DedA superfamily8; 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.Keywords
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This publication has 54 references indexed in Scilit:
- Multiple deletions reveal the essentiality of the DedA membrane protein family in Escherichia coliMicrobiology, 2012
- Mechanism of Action and Limited Cross-Resistance of New Lipopeptide MX-2401Antimicrobial Agents and Chemotherapy, 2011
- Design and Synthesis of a New Class of Membrane-Permeable Triazaborolopyridinium Fluorescent ProbesJournal of the American Chemical Society, 2011
- Inefficient Tat-Dependent Export of Periplasmic Amidases in an Escherichia coli Strain with Mutations in Two DedA Family GenesJournal of Bacteriology, 2010
- The Bacillus subtilis σM regulon and its contribution to cell envelope stress responsesMolecular Microbiology, 2008
- Structural Classification and Prediction of Reentrant Regions in α-Helical Transmembrane Proteins: Application to Complete GenomesJournal of Molecular Biology, 2006
- Cationic Antimicrobial Peptide Resistance in Neisseria meningitidisJournal of Bacteriology, 2005
- PmrAB, a Two-Component Regulatory System of Pseudomonas aeruginosa That Modulates Resistance to Cationic Antimicrobial Peptides and Addition of Aminoarabinose to Lipid AJournal of Bacteriology, 2004
- Transbilayer transport of phosphatidic acid in response to transmembrane pH gradientsBiochemistry, 1991
- Amphomycin inhibits phospho-N-acetylmuramyl-pentapeptide translocase in peptidoglycan synthesis of BacillusBiochemical and Biophysical Research Communications, 1979