Reference - Detail
| RRC ID | 35498 |
|---|---|
| Author | Zheng T, Bullock JL, Nolan EM. |
| Title | Siderophore-mediated cargo delivery to the cytoplasm of Escherichia coli and Pseudomonas aeruginosa: syntheses of monofunctionalized enterobactin scaffolds and evaluation of enterobactin-cargo conjugate uptake. |
| Journal | J Am Chem Soc |
| Abstract |
The design and syntheses of monofunctionalized enterobactin (Ent, L- and D-isomers) scaffolds where one catecholate moiety of enterobactin houses an alkene, aldehyde, or carboxylic acid at the C5 position are described. These molecules are key precursors to a family of 10 enterobactin-cargo conjugates presented in this work, which were designed to probe the extent to which the Gram-negative ferric enterobactin uptake and processing machinery recognizes, transports, and utilizes derivatized enterobactin scaffolds. A series of growth recovery assays employing enterobactin-deficient E. coli ATCC 33475 (ent-) revealed that six conjugates based on L-Ent having relatively small cargos promoted E. coli growth under iron-limiting conditions whereas negligible-to-no growth recovery was observed for four conjugates with relatively large cargos. No growth recovery was observed for the enterobactin receptor-deficient strain of E. coli H1187 (fepA-) or the enterobactin esterase-deficient derivative of E. coli K-12 JW0576 (fes-), or when the D-isomer of enterobactin was employed. These results demonstrate that the E. coli ferric enterobactin transport machinery identifies and delivers select cargo-modified scaffolds to the E. coli cytoplasm. Pseudomonas aeruginosa PAO1 K648 (pvd-, pch-) exhibited greater promiscuity than that of E. coli for the uptake and utilization of the enterobactin-cargo conjugates, and growth promotion was observed for eight conjugates under iron-limiting conditions. Enterobactin may be utilized for delivering molecular cargos via its transport machinery to the cytoplasm of E. coli and P. aeruginosa thereby providing a means to overcome the Gram-negative outer membrane permeability barrier. |
| Volume | 134(44) |
| Pages | 18388-400 |
| Published | 2012-11-7 |
| DOI | 10.1021/ja3077268 |
| PMID | 23098193 |
| MeSH | Biological Transport Enterobactin / chemistry Enterobactin / metabolism* Escherichia coli / chemistry Escherichia coli / growth & development Escherichia coli / metabolism* Escherichia coli Infections / microbiology Humans Pseudomonas Infections / microbiology Pseudomonas aeruginosa / chemistry Pseudomonas aeruginosa / growth & development Pseudomonas aeruginosa / metabolism* Siderophores / chemistry Siderophores / metabolism* |
| IF | 14.612 |
| Times Cited | 43 |
| WOS Category | CHEMISTRY, MULTIDISCIPLINARY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 11 |
| Altmetric score changes over past 6months | 0.0 |
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| Prokaryotes E. coli | NA |