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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
Antimicrobials as promoters of genetic variation
Jesús Blázquez1, Alejandro Couce, Jerónimo Rodríguez-Beltrán
1Centro Nacional de Biotecnología, Madrid, Spain. blazquez@cnb.csic.es
Abstract:
The main causes of antibiotic resistance are the selection of naturally occurring resistant variants and horizontal gene transfer processes. In recent years, the implications of antibiotic contact or treatment in drug resistance acquisition by bacteria have been gradually more evident. The ultimate source of bacterial genetic alterations to face antibiotic toxicity is mutation. All evidence points to antibiotics, especially when present at sublethal concentrations, as responsible for increasing genetic variation and therefore participating in the emergence of antibiotic resistance. Antibiotics may cause genetic changes by means of different pathways involving an increase of free radicals inside the cell or oxidative stress, by inducing error-prone polymerases mediated by SOS response, misbalancing nucleotide metabolism or acting directly on DNA. In addition, the concerted action of certain environmental conditions with subinhibitory concentrations of antimicrobials may contribute to increasing the mutagenic effect of antibiotics even more. Here we review and discuss in detail the recent advances concerning these issues and their relevance in the field of antibiotic resistance.
Insights
Antibiotics, even at low doses, can increase bacterial genetic variation and promote antibiotic resistance. This occurs through mutation and oxidative stress, accelerating the emergence of drug-resistant bacteria.
Area of Science:
- Microbiology
- Genetics
- Pharmacology
Background:
- Antibiotic resistance is a major global health threat.
- Mechanisms of resistance include selection of resistant variants and horizontal gene transfer.
- The role of antibiotics themselves in driving resistance is increasingly recognized.
Purpose of the Study:
- To review and discuss recent advances in understanding how antibiotics induce genetic variation.
- To explore the mechanisms by which antibiotics promote antibiotic resistance.
- To highlight the relevance of these findings in the context of emerging drug resistance.
Main Methods:
- Literature review of recent scientific publications.
- Analysis of studies investigating antibiotic-induced mutagenesis.
- Discussion of pathways involving oxidative stress, SOS response, and DNA damage.
Main Results:
- Antibiotics, particularly at sub-lethal concentrations, act as mutagens.
- Mechanisms include increased free radicals, oxidative stress, SOS response activation, and direct DNA damage.
- Environmental factors can potentiate the mutagenic effects of antibiotics.
Conclusions:
- Antibiotics actively contribute to the emergence of antibiotic resistance by increasing bacterial genetic variation.
- Understanding these mechanisms is crucial for developing strategies to combat antibiotic resistance.
- Further research is needed to fully elucidate the interplay between antibiotics, environmental factors, and resistance development.
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