Harnessing microbial iron chelators to develop innovative therapeutic agents
Background: Bacterial infections involving multidrug-resistant Gram-negative bacteria have become critically involved in the current antibiotic crisis. This, together with the bacterial evolution ability, prioritizes the discovery of new antibiotics. Research on microbial iron acquisition pathways a...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | Journal of Advanced Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S209012322100206X |
| _version_ | 1811238374051151872 |
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| author | Marta Ribeiro Cátia A. Sousa Manuel Simões |
| author_facet | Marta Ribeiro Cátia A. Sousa Manuel Simões |
| author_sort | Marta Ribeiro |
| collection | DOAJ |
| description | Background: Bacterial infections involving multidrug-resistant Gram-negative bacteria have become critically involved in the current antibiotic crisis. This, together with the bacterial evolution ability, prioritizes the discovery of new antibiotics. Research on microbial iron acquisition pathways and metabolites, particularly siderophores, has highlighted hopeful aspects for the design of advanced antimicrobial approaches. Moreover, exploiting siderophores machinery to treat diseases associated with iron overload and cancer is of additional interest for the therapeutic arena. Aim of Review: This review highlights and provides a renewed perspective on the evolutionary path of siderophores, from primordial siderophores to new iron chelating agents, stimulating the field to build on the past and shape the future. Key Scientific Concepts of Review: The effectiveness of siderophore-mimicking antibiotics appears to be high and selective for Gram-negative pathogens, rendering multidrug-resistant (MDR) bacteria susceptible to killing. Herein, cefiderocol, a new siderophore antibiotic, is well positioned in the clinic to treat MDR infections instigated by Gram-negative bacteria, particularly urinary tract infections and pneumonia. This siderophore has a mode of action based on a “Trojan horse” strategy, using the iron uptake systems for efficient bacterial penetration and killing. Recent progress has also been achieved concerning new iron chelating compounds to treat diseases associated with iron overload and cancer. Though these compounds still face great challenges for a clinical application, their promising results open up new doors for the design and development of innovative iron chelating compounds, taking benefit from the structurally diverse nature of siderophores. |
| first_indexed | 2024-04-12T12:41:45Z |
| format | Article |
| id | doaj.art-8d5535ed35f644a19bf12fe2367a72e2 |
| institution | Directory Open Access Journal |
| issn | 2090-1232 |
| language | English |
| last_indexed | 2024-04-12T12:41:45Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj.art-8d5535ed35f644a19bf12fe2367a72e22022-12-22T03:32:46ZengElsevierJournal of Advanced Research2090-12322022-07-013989101Harnessing microbial iron chelators to develop innovative therapeutic agentsMarta Ribeiro0Cátia A. Sousa1Manuel Simões2LEPABE – Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; CIQUP – Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, PortugalLEPABE – Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, PortugalLEPABE – Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; Corresponding author.Background: Bacterial infections involving multidrug-resistant Gram-negative bacteria have become critically involved in the current antibiotic crisis. This, together with the bacterial evolution ability, prioritizes the discovery of new antibiotics. Research on microbial iron acquisition pathways and metabolites, particularly siderophores, has highlighted hopeful aspects for the design of advanced antimicrobial approaches. Moreover, exploiting siderophores machinery to treat diseases associated with iron overload and cancer is of additional interest for the therapeutic arena. Aim of Review: This review highlights and provides a renewed perspective on the evolutionary path of siderophores, from primordial siderophores to new iron chelating agents, stimulating the field to build on the past and shape the future. Key Scientific Concepts of Review: The effectiveness of siderophore-mimicking antibiotics appears to be high and selective for Gram-negative pathogens, rendering multidrug-resistant (MDR) bacteria susceptible to killing. Herein, cefiderocol, a new siderophore antibiotic, is well positioned in the clinic to treat MDR infections instigated by Gram-negative bacteria, particularly urinary tract infections and pneumonia. This siderophore has a mode of action based on a “Trojan horse” strategy, using the iron uptake systems for efficient bacterial penetration and killing. Recent progress has also been achieved concerning new iron chelating compounds to treat diseases associated with iron overload and cancer. Though these compounds still face great challenges for a clinical application, their promising results open up new doors for the design and development of innovative iron chelating compounds, taking benefit from the structurally diverse nature of siderophores.http://www.sciencedirect.com/science/article/pii/S209012322100206XAntibiotic resistanceBiofilmsCancer therapyIron overloadSiderophoresTrojan horse |
| spellingShingle | Marta Ribeiro Cátia A. Sousa Manuel Simões Harnessing microbial iron chelators to develop innovative therapeutic agents Journal of Advanced Research Antibiotic resistance Biofilms Cancer therapy Iron overload Siderophores Trojan horse |
| title | Harnessing microbial iron chelators to develop innovative therapeutic agents |
| title_full | Harnessing microbial iron chelators to develop innovative therapeutic agents |
| title_fullStr | Harnessing microbial iron chelators to develop innovative therapeutic agents |
| title_full_unstemmed | Harnessing microbial iron chelators to develop innovative therapeutic agents |
| title_short | Harnessing microbial iron chelators to develop innovative therapeutic agents |
| title_sort | harnessing microbial iron chelators to develop innovative therapeutic agents |
| topic | Antibiotic resistance Biofilms Cancer therapy Iron overload Siderophores Trojan horse |
| url | http://www.sciencedirect.com/science/article/pii/S209012322100206X |
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