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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
The ability of certain antimutagenic agents to prevent development of antibiotic resistance
S P Pillai1, C A Pillai, D M Shankel
1Department of Medicinal Chemistry, University of Kansas, 6048 Haworth Hall, 1200 Sunnyside, Lawrence, KS 66045-7534, USA. shankel@ukans.edu
Abstract:
Resistance to multiple antimicrobial agents has now become a prominent fact of contemporary life. It is believed that poor patient compliance, e.g. interrupted or premature cessation of therapy; and misuse or abuse of antibiotics, e.g. wrong antibiotic or insufficient dose, play important roles in resistance development. We present evidence that, this form of resistance often stems from spontaneous mutations accompanied by the positive selecting pressure of the doses of antibiotics being between the MIC and MBC levels. A number of antimutagenic agents, e.g. green tea catechins, and other antioxidants, etc. are able to suppress the emergence of resistance. In many cases, these agents are capable of exerting these effects at doses which by themselves produce no visible effect on growth. In a number of cases antimutagenic substances capable of preventing resistance emergence are present in normal food stuffs. These effects are exerted against resistance to tetracyclines, fluoroquinolones, macrolides, beta-lactams, aminoglycosides and the like. The implications of these laboratory findings for practical chemotherapy are discussed.
Insights
Antimicrobial resistance emerges from mutations amplified by antibiotic exposure. Certain natural compounds, like green tea catechins, can suppress this resistance development without affecting bacterial growth.
Area of Science:
- Microbiology
- Pharmacology
- Genetics
Background:
- Antimicrobial resistance is a significant global health challenge.
- Poor patient compliance and antibiotic misuse are major contributors to resistance.
- Spontaneous mutations under specific antibiotic concentrations drive resistance emergence.
Purpose of the Study:
- To investigate the role of spontaneous mutations and antibiotic concentrations in resistance development.
- To explore the potential of antimutagenic agents in preventing antimicrobial resistance.
- To examine the efficacy of natural compounds against various classes of antibiotics.
Main Methods:
- Studying spontaneous mutations in bacteria exposed to sub-inhibitory antibiotic concentrations.
- Evaluating the effects of antimutagenic agents, including green tea catechins and antioxidants.
- Testing the impact of these agents on resistance to tetracyclines, fluoroquinolones, macrolides, beta-lactams, and aminoglycosides.
Main Results:
- Antibiotic resistance frequently arises from spontaneous mutations under specific antibiotic selective pressures (between MIC and MBC levels).
- Antimutagenic agents, such as green tea catechins and antioxidants, effectively suppress the emergence of antimicrobial resistance.
- These beneficial effects are observed even at doses that do not inhibit bacterial growth, and some agents are found in common foods.
Conclusions:
- Spontaneous mutations coupled with specific antibiotic dosing are key drivers of antimicrobial resistance.
- Natural antimutagenic compounds offer a promising strategy to combat resistance development.
- Dietary components may play a role in preventing resistance to a wide range of essential antibiotics, with implications for chemotherapy.
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