Metallotherapeutics development in the age of iron-clad bacteria
| Autor: | Angela Wilks, Garrick Centola, Fengtian Xue |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Siderophore Porphyrins medicine.drug_class Iron 030106 microbiology Antibiotics Biophysics Siderophores Gallium medicine.disease_cause Biochemistry Article Biomaterials 03 medical and health sciences Drug Discovery Global health medicine Animals Humans Significant risk Iron uptake biology Bacteria business.industry Metals and Alloys Pathogenic bacteria Bacterial Infections biology.organism_classification Iron source Biotechnology Anti-Bacterial Agents 030104 developmental biology Chemistry (miscellaneous) business |
| Zdroj: | Metallomics |
| ISSN: | 1756-591X |
| Popis: | Drug-resistant infections pose a significant risk to global health as pathogenic bacteria become increasingly difficult to treat. The rapid selection of resistant strains through poor antibiotic stewardship has reduced the number of viable treatments and increased morbidity of infections, especially among the immunocompromised. To circumvent such challenges, new strategies are required to stay ahead of emerging resistance trends, yet research and funding for antibiotic development lags other classes of therapeutics. Though the use of metals in therapeutics has been around for centuries, recent strategies have devoted a great deal of effort into the pathways through which bacteria acquire and utilize iron, which is critical for the establishment of infection. To target iron uptake systems, siderophore–drug conjugates have been developed that hijack siderophore-based iron uptake for delivery of antibiotics. While this strategy has produced several potential leads, the use of siderophores in infection is diminished over time when bacteria adapt to utilize heme as an iron source, leading to a need for the development of porphyrin mimetics as therapeutics. The use of such strategies as well as the inclusion of gallium, a redox-inert iron mimic, are herein reviewed. |
| Databáze: | OpenAIRE |
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