Synthesis of lipid-linked precursors of the bacterial cell wall is governed by a feedback control mechanism in Pseudomonas aeruginosa.

LS Marmont, AK Orta, BWA Baileeves, D Sychantha, A Fernández-Galliano, Yancheng Li, NG Greene, RA Corey, PJ Stansfeld, WM Clemons, TG Bernhardt*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

1 Citation (Scopus)

Abstract

Many bacterial surface glycans such as the peptidoglycan (PG) cell wall are built from monomeric units linked to a polyprenyl lipid carrier. How this limiting carrier is distributed among competing pathways has remained unclear. Here we describe the isolation of hyperactive variants of Pseudomonas aeruginosa MraY, the enzyme that forms the first lipid-linked PG precursor. These variants result in the elevated production of the final PG precursor lipid II in cells and are hyperactive in vitro. The activated MraY variants have substitutions that map to a cavity on the extracellular side of the dimer interface, far from the active site. Our structural and molecular dynamics results suggest that this cavity is a binding site for externalized lipid II. Overall, our results support a model in which excess externalized lipid II allosterically inhibits MraY, providing a feedback mechanism that prevents the sequestration of lipid carrier in the PG biogenesis pathway.
Original languageEnglish
Pages (from-to)763-775
Number of pages13
JournalNature Microbiology
Volume9
Issue number3
Early online date9 Feb 2024
DOIs
Publication statusPublished - 1 Mar 2024

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© The Author(s) 2024.

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