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General mechanisms of resistance to antibiotics
1Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Alberta, Canada.
Abstract:
Resistance to antimicrobial agents may result from intrinsic properties of organisms, through mutation and through plasmid- and transposon-specified genes. beta-Lactam resistance is most frequently associated with one or more chromosomal- or plasmid-specified beta-lactamases. Recently, mutations modifying penicillin-binding proteins have been detected with increased frequency as a cause of beta-lactam resistance. Mixed mechanisms, reduced permeability and tolerance are other causes of resistance. Aminoglycoside resistance always involves some modification of drug uptake, most often due to a variety of enzymes modifying these compounds. Reduced uptake is a primary cause of resistance in anaerobic bacteria and bacteria growing anaerobically, some strains of Pseudomonas aeruginosa, and mutants that arise during antimicrobial therapy and are defective in energy-generation systems. Resistance to other antimicrobial agents is presented in tabular form.
Insights
Antimicrobial resistance arises from genetic mutations and gene transfers, leading to mechanisms like beta-lactamase production and altered drug targets. Understanding these resistance pathways is crucial for effective antimicrobial therapy.
Area of Science:
- Microbiology
- Molecular Biology
- Pharmacology
Background:
- Antimicrobial resistance (AMR) poses a significant global health threat.
- Mechanisms of resistance are diverse, involving intrinsic factors, mutations, and mobile genetic elements.
- Beta-lactam and aminoglycoside resistance are common and clinically relevant.
Purpose of the Study:
- To review the multifaceted mechanisms of antimicrobial resistance.
- To highlight key resistance pathways for beta-lactam and aminoglycoside antibiotics.
- To provide a comprehensive overview of factors contributing to AMR.
Main Methods:
- Literature review of antimicrobial resistance mechanisms.
- Analysis of genetic and biochemical pathways conferring resistance.
- Tabular presentation of resistance to various antimicrobial agents.
Main Results:
- Beta-lactam resistance often involves beta-lactamases or modified penicillin-binding proteins.
- Aminoglycoside resistance typically results from enzymatic modification or reduced drug uptake.
- Reduced permeability and altered energy generation systems also contribute to resistance.
Conclusions:
- Antimicrobial resistance is driven by a combination of genetic and physiological adaptations.
- Diverse mechanisms necessitate a thorough understanding for developing new therapeutic strategies.
- Effective antimicrobial stewardship requires knowledge of evolving resistance patterns.