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E-Book 3rd Congress

  • The effect of epigenetic changes on antibiotic resistance: DNA methylation
  • Seyed Ali Sadr Tabatabaee,1 Maryam Mashhadi Abolghasem Shirazi,2,*
    1. Bachelor’s student, Microbiology group, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
    2. Department of Microbiology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran Molecular Virology Department, Pasteur Institute of Iran, Tehran, Iran


  • Introduction: Antibiotic resistance has become a global health crisis, threatening the effectiveness of our most valuable weapon against bacterial infections - antibiotics. The emergence and spread of antibiotic resistance have been extensively studied, but recent research suggests that there may be more to the story than previously thought. Epigenetics, the study of heritable changes in gene expression that do not involve alterations in the DNA sequence, is now being recognized as a potential player in the development of antibiotic resistance in bacteria.
  • Methods: This article uses an extensive search of PubMed - NCBI and Google Scholar databases - and the study of almost 30 articles and an analysis of the studies done in the last ten years on this issue.
  • Results: Epigenetic modifications, such as DNA methylation and histone modifications, can influence gene expression patterns and cellular responses to antibiotics. These modifications serve as a regulatory mechanism that allows bacteria to adapt to changing environments and survive antibiotic exposure. The dynamic nature of epigenetic modifications provides bacteria with the ability to rapidly switch between susceptible and resistant phenotypes, contributing to the high-paced emergence of drug resistance. DNA methylation, the addition of a methyl group to DNA bases, has been shown to play a role in antibiotic resistance. Methylation of adenines can influence mutation rates in bacterial genomes, leading to changes in antibiotic susceptibility. For example, methylation of specific adenines in the DNA repair gene can enhance bacterial survival under antibiotic stress by reducing deleterious mutations. On the other hand, cytosine methylation has been linked to reduced expression of resistance-conferring genes, resulting in poor survival under antibiotic stress. Histone modifications, such as acetylation and methylation, can also impact gene expression in bacteria. These modifications alter the structure of chromatin, influencing the accessibility of genes to the transcriptional machinery. Studies have shown that histone modifications can regulate the expression of genes involved in antibiotic resistance, including efflux pumps and drug targets. By modulating gene expression, histone modifications contribute to the development of antibiotic resistance in bacteria. Several epigenetic mechanisms have been identified as potential contributors to antibiotic resistance in bacteria. These mechanisms include the activity of methyltransferases, the presence of methylated cytosines in promoter regions, and the integration of methyltransferase-encoding phages into bacterial genomes. Adaptive resistance, also known as tolerance, is a phenomenon in which bacteria acquire the ability to survive in the presence of subinhibitory concentrations of antibiotics. This form of resistance is reversible and can be lost when the antibiotic is withdrawn. Epigenetic changes have been implicated in the modulation of gene expression patterns that allow bacteria to switch between susceptible and resistant phenotypes, contributing to the development of adaptive resistance. Bacterial persistence, characterized by the presence of a small subpopulation of dormant cells that are tolerant to antibiotics, is another mechanism by which bacteria can survive antibiotic exposure. Epigenetic inheritance has been proposed as a key player in phenotypic drug tolerance in persisters; The dynamic nature of epigenetic modifications allows for the generation of a seed bank of persister cells that can survive rapidly changing environments, leading to the adaptive evolution of drug-resistant mutants. Targeting epigenetic modifications could provide a means to overcome antibiotic resistance and enhance the efficacy of existing antibiotics. Additionally, understanding the epigenetic mechanisms underlying antibiotic resistance could help in the development of new diagnostic tools and strategies for the prevention and management of antibiotic-resistant infections The dynamic and reversible nature of epigenetic modifications provides bacteria with the ability to rapidly adapt to antibiotic exposure and survive under challenging conditions.
  • Conclusion: Further research is needed to fully understand the complex interplay between epigenetics and antibiotic resistance and to explore the potential of targeting epigenetic mechanisms for the development of new therapeutic approaches. By unraveling the intricate connection between antibiotic resistance and epigenetics, we may be able to combat the rising tide of antibiotic-resistant bacteria and preserve the effectiveness of our arsenal against infectious diseases.
  • Keywords: Epigenetic/DNA methylation /histone modifications