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Evolution and spread of antibiotic resistance
B Henriques Normark1, S Normark
1Swedish Institute of Infectious Disease Control and the Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Abstract:
Antibiotic resistance is a clinical and socioeconomical problem that is here to stay. Resistance can be natural or acquired. Some bacterial species, such as Pseudomonas aeruginosa, show a high intrinsic resistance to a number of antibiotics whereas others are normally highly antibiotic susceptible such as group A streptococci. Acquired resistance evolve via genetic alterations in the microbes own genome or by horizontal transfer of resistance genes located on various types of mobile DNA elements. Mutation frequencies to resistance can vary dramatically depending on the mechanism of resistance and whether or not the organism exhibits a mutator phenotype. Resistance usually has a biological cost for the microorganism, but compensatory mutations accumulate rapidly that abolish this fitness cost, explaining why many types of resistances may never disappear in a bacterial population. Resistance frequently occurs stepwise making it important to identify organisms with low level resistance that otherwise may constitute the genetic platform for development of higher resistance levels. Self-replicating plasmids, prophages, transposons, integrons and resistance islands all represent DNA elements that frequently carry resistance genes into sensitive organisms. These elements add DNA to the microbe and utilize site-specific recombinases/integrases for their integration into the genome. However, resistance may also be created by homologous recombination events creating mosaic genes where each piece of the gene may come from a different microbe. The selection with antibiotics have informed us much about the various genetic mechanisms that are responsible for microbial evolution.
Insights
Antibiotic resistance, a growing clinical and socioeconomic issue, arises from natural or acquired genetic changes in bacteria. Understanding these mechanisms is crucial for combating resistance evolution in microbial populations.
Area of Science:
- Microbiology
- Genetics
- Evolutionary Biology
Background:
- Antibiotic resistance poses a significant clinical and socioeconomic challenge.
- Bacterial resistance can be intrinsic (e.g., Pseudomonas aeruginosa) or acquired.
- Acquired resistance develops through genomic alterations or horizontal gene transfer.
Purpose of the Study:
- To explore the genetic mechanisms underlying antibiotic resistance evolution in bacteria.
- To highlight the role of mobile genetic elements and recombination in spreading resistance.
- To emphasize the importance of identifying low-level resistance for preventing higher resistance development.
Main Methods:
- Review of genetic mechanisms of antibiotic resistance.
- Analysis of bacterial evolution under antibiotic selection.
- Examination of mobile DNA elements (plasmids, transposons, integrons) and recombination events.
Main Results:
- Resistance evolves via mutations and horizontal gene transfer, facilitated by mobile genetic elements.
- Compensatory mutations can overcome the fitness cost of resistance, ensuring its persistence.
- Stepwise acquisition of resistance and homologous recombination contribute to complex resistance patterns.
Conclusions:
- Antibiotic resistance is a dynamic evolutionary process driven by genetic changes and selection pressures.
- Understanding resistance mechanisms is vital for developing strategies to mitigate its impact.
- Continuous monitoring and research are necessary to address the evolving threat of antibiotic resistance.