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-Structure paper
| タイトル | L-type pyocins inhibit the BAM complex to kill without cell entry. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Year 2026 |
| 掲載日 | 2026年7月2日 |
著者 | Fabian Munder / Matthew D Johnson / Imogen Samuels / Laura McCaughey / Oleksii Zdorevskyi / Chunxiao Wang / Ashleigh Kropp / Lauren Zavan / Erin P Price / Derek S Sarovich / Swati Varshney / Christopher A McDevitt / Hari Venugopal / Vivek Sharma / Matthew T Doyle / Francesca Short / Debnath Ghosal / James P R Connolly / Gavin J Knott / Rhys Grinter / ![]() |
| PubMed 要旨 | Many antibiotics are ineffective against the Gram-negative pathogen Pseudomonas aeruginosa because of intrinsic defence mechanisms, such as the impermeable bacterial outer membrane. Here, we show ...Many antibiotics are ineffective against the Gram-negative pathogen Pseudomonas aeruginosa because of intrinsic defence mechanisms, such as the impermeable bacterial outer membrane. Here, we show that protein antibiotics called L-type pyocins kill P. aeruginosa by inhibiting the β-barrel assembly machinery (BAM) complex at the cell surface, halting outer-membrane protein assembly. Using single-particle cryo-electron microscopy, we show that L-type pyocins bind a surface-exposed region of BamA and deploy a C-terminal peptide that competitively inhibits the BAM complex, demonstrating that cell entry is not required for antibiotic activity. We combine genetics, multi-omics and cryo-electron tomography to show that BAM complex inhibition by L-type pyocins or the cyclic-peptide antibiotic, darobactin, triggers a multifaceted transcriptomic, proteomic, and morphological response. BAM inhibition ultimately leads to a catastrophic loss of membrane integrity and cell death. These results validate BAM as a target for antibiotics that do not enter the cell and define an engineerable system for their development. |
リンク | Nat Commun / PubMed:42393045 |
| 手法 | EM (単粒子) |
| 解像度 | 2.75 - 3.18 Å |
| 構造データ | EMDB-71969, PDB-9pxg: EMDB-71970, PDB-9pxi: EMDB-71971, PDB-9pxj: |
| 化合物 | ![]() ChemComp-NA: |
| 由来 |
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キーワード | MEMBRANE PROTEIN / protein complex / outer membrane / beta-barrel / protein folding / Gram-negative bacterial protein / L-type bacteriocin / pyocin |
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