Refuse in order to resist: metabolic bottlenecks reduce antibiotic susceptibility
The growth of pathogenic bacteria in the host is a prerequisite for infectious diseases. Antibiotic drugs are used to impair bacterial growth and thereby treat infections. In turn, growth of bacteria is underpinned by their primary metabolism. Thus, it has long been recognized that the activity of a...
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| Format: | Article |
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Springer Nature
2025-02-01
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| Series: | Molecular Systems Biology |
| Online Access: | https://doi.org/10.1038/s44320-025-00089-2 |
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| author | Orestis Kanaris Frank Schreiber |
| author_facet | Orestis Kanaris Frank Schreiber |
| author_sort | Orestis Kanaris |
| collection | DOAJ |
| description | The growth of pathogenic bacteria in the host is a prerequisite for infectious diseases. Antibiotic drugs are used to impair bacterial growth and thereby treat infections. In turn, growth of bacteria is underpinned by their primary metabolism. Thus, it has long been recognized that the activity of antibiotics is determined by the metabolic state of cells. However, only recently researchers have begun to systematically interrogate the links between metabolism and resistance (Jiang et al, 2023; Lopatkin et al, 2021; Pinheiro et al, 2021; Schrader et al, 2021; Zhao et al, 2021). In their recent study, Lubrano and colleagues (Lubrano et al, 2025) apply an elegant CRISPR-based approach to the model bacterium Escherichia coli to systematically screen the effect of 15,120 mutations in genes that encode for 346 proteins which are required for growth of E. coli (also referred to as ‘essential proteins’). The authors identified a multitude of mutations that reduce the susceptibility against two antibiotics related to two very distinct chemical classes; the β-lactam antibiotic carbenicillin and the aminoglycoside gentamicin. Strikingly, the majority of the identified mutations are directly linked to primary metabolism. The work highlights the importance of metabolism in order to understand antibiotic resistance mechanisms and the ecology and evolution of antibiotic resistance. In addition, the work provides leads to design metabolism-based intervention strategies to mitigate antibiotic resistance. |
| format | Article |
| id | doaj-art-22c5e4fd6feb4d5a9e41f0f42a694308 |
| institution | OA Journals |
| issn | 1744-4292 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-22c5e4fd6feb4d5a9e41f0f42a6943082025-08-20T01:57:40ZengSpringer NatureMolecular Systems Biology1744-42922025-02-0121321121310.1038/s44320-025-00089-2Refuse in order to resist: metabolic bottlenecks reduce antibiotic susceptibilityOrestis Kanaris0Frank Schreiber1Division Biodeterioration and Reference Organisms, Department of Materials and the Environment, Federal Institute for Materials Research and TestingDivision Biodeterioration and Reference Organisms, Department of Materials and the Environment, Federal Institute for Materials Research and TestingThe growth of pathogenic bacteria in the host is a prerequisite for infectious diseases. Antibiotic drugs are used to impair bacterial growth and thereby treat infections. In turn, growth of bacteria is underpinned by their primary metabolism. Thus, it has long been recognized that the activity of antibiotics is determined by the metabolic state of cells. However, only recently researchers have begun to systematically interrogate the links between metabolism and resistance (Jiang et al, 2023; Lopatkin et al, 2021; Pinheiro et al, 2021; Schrader et al, 2021; Zhao et al, 2021). In their recent study, Lubrano and colleagues (Lubrano et al, 2025) apply an elegant CRISPR-based approach to the model bacterium Escherichia coli to systematically screen the effect of 15,120 mutations in genes that encode for 346 proteins which are required for growth of E. coli (also referred to as ‘essential proteins’). The authors identified a multitude of mutations that reduce the susceptibility against two antibiotics related to two very distinct chemical classes; the β-lactam antibiotic carbenicillin and the aminoglycoside gentamicin. Strikingly, the majority of the identified mutations are directly linked to primary metabolism. The work highlights the importance of metabolism in order to understand antibiotic resistance mechanisms and the ecology and evolution of antibiotic resistance. In addition, the work provides leads to design metabolism-based intervention strategies to mitigate antibiotic resistance.https://doi.org/10.1038/s44320-025-00089-2 |
| spellingShingle | Orestis Kanaris Frank Schreiber Refuse in order to resist: metabolic bottlenecks reduce antibiotic susceptibility Molecular Systems Biology |
| title | Refuse in order to resist: metabolic bottlenecks reduce antibiotic susceptibility |
| title_full | Refuse in order to resist: metabolic bottlenecks reduce antibiotic susceptibility |
| title_fullStr | Refuse in order to resist: metabolic bottlenecks reduce antibiotic susceptibility |
| title_full_unstemmed | Refuse in order to resist: metabolic bottlenecks reduce antibiotic susceptibility |
| title_short | Refuse in order to resist: metabolic bottlenecks reduce antibiotic susceptibility |
| title_sort | refuse in order to resist metabolic bottlenecks reduce antibiotic susceptibility |
| url | https://doi.org/10.1038/s44320-025-00089-2 |
| work_keys_str_mv | AT orestiskanaris refuseinordertoresistmetabolicbottlenecksreduceantibioticsusceptibility AT frankschreiber refuseinordertoresistmetabolicbottlenecksreduceantibioticsusceptibility |