Catechol-substituted siderophore colistin exhibits superior antimicrobial activity than its unmodified polypeptide counterpart
Abstract Catechol moieties have been covalently coupled to the last-resort polypeptide antibiotic colistin via esterification and amidation reactions, inspired by the superior antimicrobial action of cefiderocol, i.e., a catechol-substituted siderophore cephalosporin. Among the tested strategies, th...
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BMC
2025-06-01
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| Series: | BMC Chemistry |
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| Online Access: | https://doi.org/10.1186/s13065-025-01538-7 |
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| author | Sara Bescós-Ramo Enrique Gámez María del Mar Encabo-Berzosa Milagros Piñol Luis Oriol Manuel Arruebo |
| author_facet | Sara Bescós-Ramo Enrique Gámez María del Mar Encabo-Berzosa Milagros Piñol Luis Oriol Manuel Arruebo |
| author_sort | Sara Bescós-Ramo |
| collection | DOAJ |
| description | Abstract Catechol moieties have been covalently coupled to the last-resort polypeptide antibiotic colistin via esterification and amidation reactions, inspired by the superior antimicrobial action of cefiderocol, i.e., a catechol-substituted siderophore cephalosporin. Among the tested strategies, the incorporation of the catechol motif by amidation reduces by 50% the minimum concentration to inhibit the growth of a clinical strain of uropathogenic Escherichia coli (E. coli) in its planktonic form. Its minimum bactericidal concentration is reduced by 25% after chemical modification. The tested modified antibiotic did not show cytotoxicity against human fibroblasts and keratinocytes at bactericidal doses. Additionally, due to the potential nephrotoxicity of colistin, the cytotoxicity of this catechol-substituted siderophore colistin was evaluated in a 3D model of human renal organoids showing no cytotoxicity at the doses tested. The chemical incorporation of catechol groups to existing antibiotics can reduce the doses to exert a fast antimicrobial action reducing the chances to develop antibiotic resistance. |
| format | Article |
| id | doaj-art-8cc0782aafaa429783fe56ebd24ec894 |
| institution | DOAJ |
| issn | 2661-801X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Chemistry |
| spelling | doaj-art-8cc0782aafaa429783fe56ebd24ec8942025-08-20T02:40:14ZengBMCBMC Chemistry2661-801X2025-06-0119111410.1186/s13065-025-01538-7Catechol-substituted siderophore colistin exhibits superior antimicrobial activity than its unmodified polypeptide counterpartSara Bescós-Ramo0Enrique Gámez1María del Mar Encabo-Berzosa2Milagros Piñol3Luis Oriol4Manuel Arruebo5Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de ZaragozaInstituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de ZaragozaInstituto Aragonés de Ciencias de la Salud (IACS)Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de ZaragozaInstituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de ZaragozaInstituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de ZaragozaAbstract Catechol moieties have been covalently coupled to the last-resort polypeptide antibiotic colistin via esterification and amidation reactions, inspired by the superior antimicrobial action of cefiderocol, i.e., a catechol-substituted siderophore cephalosporin. Among the tested strategies, the incorporation of the catechol motif by amidation reduces by 50% the minimum concentration to inhibit the growth of a clinical strain of uropathogenic Escherichia coli (E. coli) in its planktonic form. Its minimum bactericidal concentration is reduced by 25% after chemical modification. The tested modified antibiotic did not show cytotoxicity against human fibroblasts and keratinocytes at bactericidal doses. Additionally, due to the potential nephrotoxicity of colistin, the cytotoxicity of this catechol-substituted siderophore colistin was evaluated in a 3D model of human renal organoids showing no cytotoxicity at the doses tested. The chemical incorporation of catechol groups to existing antibiotics can reduce the doses to exert a fast antimicrobial action reducing the chances to develop antibiotic resistance.https://doi.org/10.1186/s13065-025-01538-7ColistinAntibioticCatecholSiderophorePolymyxin EEsterification |
| spellingShingle | Sara Bescós-Ramo Enrique Gámez María del Mar Encabo-Berzosa Milagros Piñol Luis Oriol Manuel Arruebo Catechol-substituted siderophore colistin exhibits superior antimicrobial activity than its unmodified polypeptide counterpart BMC Chemistry Colistin Antibiotic Catechol Siderophore Polymyxin E Esterification |
| title | Catechol-substituted siderophore colistin exhibits superior antimicrobial activity than its unmodified polypeptide counterpart |
| title_full | Catechol-substituted siderophore colistin exhibits superior antimicrobial activity than its unmodified polypeptide counterpart |
| title_fullStr | Catechol-substituted siderophore colistin exhibits superior antimicrobial activity than its unmodified polypeptide counterpart |
| title_full_unstemmed | Catechol-substituted siderophore colistin exhibits superior antimicrobial activity than its unmodified polypeptide counterpart |
| title_short | Catechol-substituted siderophore colistin exhibits superior antimicrobial activity than its unmodified polypeptide counterpart |
| title_sort | catechol substituted siderophore colistin exhibits superior antimicrobial activity than its unmodified polypeptide counterpart |
| topic | Colistin Antibiotic Catechol Siderophore Polymyxin E Esterification |
| url | https://doi.org/10.1186/s13065-025-01538-7 |
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