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, Mohammed Elbediwi Evolutionary Biology, Institute for Biology, Freie Universität Berlin , 14195 Berlin , Germany Animal Health Research Institute, Agriculture Research Centre , 12618 Cairo , Egypt Corresponding author. E-mail: mohammed.elbediwi@fu-berlin.de Search for other works by this author on: Oxford Academic Jens Rolff Evolutionary Biology, Institute for Biology, Freie Universität Berlin , 14195 Berlin , Germany Berlin-Brandenburg Institute of Advanced Biodiversity Research (BBIB) , Berlin , Germany Search for other works by this author on: Oxford Academic
https://orcid.org/0000-0003-3834-8523 Journal of Antimicrobial Chemotherapy, dkae128, https://doi.org/10.1093/jac/dkae128
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14 May 2024
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Mohammed Elbediwi, Jens Rolff, Metabolic pathways and antimicrobial peptide resistance in bacteria, Journal of Antimicrobial Chemotherapy, 2024;, dkae128, https://doi.org/10.1093/jac/dkae128
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Abstract
Antimicrobial resistance is a pressing concern that poses a significant threat to global public health, necessitating the exploration of alternative strategies to combat drug-resistant microbial infections. Recently, antimicrobial peptides (AMPs) have gained substantial attention as possible replacements for conventional antibiotics. Because of their pharmacodynamics and killing mechanisms, AMPs display a lower risk of bacterial resistance evolution compared with most conventional antibiotics. However, bacteria display different mechanisms to resist AMPs, and the role of metabolic pathways in the resistance mechanism is not fully understood. This review examines the intricate relationship between metabolic genes and AMP resistance, focusing on the impact of metabolic pathways on various aspects of resistance. Metabolic pathways related to guanosine pentaphosphate (pppGpp) and guanosine tetraphosphate (ppGpp) [collectively (p)ppGpp], the tricarboxylic acid (TCA) cycle, haem biosynthesis, purine and pyrimidine biosynthesis, and amino acid and lipid metabolism influence in different ways metabolic adjustments, biofilm formation and energy production that could be involved in AMP resistance. By targeting metabolic pathways and their associated genes, it could be possible to enhance the efficacy of existing antimicrobial therapies and overcome the challenges exhibited by phenotypic (recalcitrance) and genetic resistance toward AMPs. Further research in this area is needed to provide valuable insights into specific mechanisms, uncover novel therapeutic targets, and aid in the fight against antimicrobial resistance.
© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/pages/standard-publication-reuse-rights)
Topic:
- antibiotics
- phenotype
- amino acids
- fat metabolism
- biofilms
- drug resistance, microbial
- genes
- guanosine pentaphosphate
- guanosine tetraphosphate
- purines
- pyrimidines
- tricarboxylic acids
- infections
- bacteria
- genetics
- public health medicine
- pharmacodynamics
- antimicrobials
- risk reduction
- bacterial resistance
- heme biosynthesis
- biosynthesis
- killing
- antimicrobial peptide
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