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Epigenetic and Metabolic Reprogramming Driving Multidrug Resistance in Clinically Relevant Gram-Negative Bacteria | ||
| Al-Zahraa Journal for Health and Medical Sciences | ||
| Volume 4, Issue 2, June 2026, Pages 95-113 PDF (679.25 K) | ||
| Document Type: Review Article | ||
| DOI: 10.66723/zjhms.2026.169981.1111 | ||
| Authors | ||
| Fatima A. Al-Hadidi1; Niran Adnan Aljoboury1; Doaa Ali AL shemari* 2 | ||
| 1Department of Biology, College of Sciences, University of Kerbala, Karbala, Iraq | ||
| 2University of Kerbala | ||
| Abstract | ||
| Multidrug-resistant (MDR) Gram-negative bacteria owing to epigenetic and metabolic modifications as well as genetic alterations are a major global health concern. This review aims to clarify besides classical genetic factors the roles of epigenetic mechanisms and metabolic reprogramming in antimicrobial resistance. It focuses on epigenetic mechanisms such as DNA methylation, nucleoid-associated proteins, small regulatory RNAs and phase variation that alter gene expression and lead to antimicrobial tolerance. In parallel, it highlights metabolic adaptations such as changes in carbon metabolism, redox homeostasis, efflux systems, biofilm formation, and persistence pathways that contribute to bacterial survival under antibiotic stress. The review emphasizes the role of metabolic state transitions in phenotypic resistance and virulence in clinically relevant pathogens like Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Host-pathogen interactions, clinical environmental pressures, and stress-induced regulatory networks that lead to both transient and stable resistance are also discussed. The importance of advances in multi-omics technologies for identifying non-genetic predictors of resistance is emphasized. In summary, the interplay between epigenetic and metabolic plasticity offers a novel paradigm for predicting resistance evolution and designing new therapeutic strategies, for example by targeting bacterial metabolism and epigenetic systems as alternatives to conventional antibiotics. | ||
| Keywords | ||
| key words: tricarboxylic acid (TCA); deoxyribonucleic acid; phase variation; Genetic mutation transcriptional inhibitors; Pseudomonas aeruginosa | ||
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