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Mode of incomplete cross-resistance among pipemidic, piromidic, and nalidixic acids
Abstract:
Spontaneous mutants with various patterns of resistance to pipemidic acid (PPA), piromidic acid (PA), and nalidixic acid (NAL) were isolated from Escherichia coli K-12. Most mutants were less resistant to PPA than to PA and NAL, and some mutants resistant to PA and NAL were hypersusceptible to PPA. As for the mutants tested, resistance to the drugs was conferred by mutations at nalA and new nal genes designated as nalC and nalD, both of which were located at about 82 min on the recalibrated map. Resistance to PA and NAL was due to decreased sensitivity of the bacterial DNA synthesizing system to them and insufficient drug transport, whereas resistance to PPA was only due to the former.
Insights
Researchers studied Escherichia coli K-12 mutants resistant to quinolone antibiotics like pipemidic acid (PPA), piromidic acid (PA), and nalidixic acid (NAL). Mutations in specific genes conferred resistance, with varying susceptibility patterns observed for different drugs.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Quinolone antibiotics, including pipemidic acid (PPA), piromidic acid (PA), and nalidixic acid (NAL), are crucial in treating bacterial infections.
- Understanding the mechanisms of bacterial resistance to these drugs is essential for developing effective therapeutic strategies.
- Escherichia coli K-12 serves as a model organism for studying bacterial genetics and antibiotic resistance.
Purpose of the Study:
- To isolate and characterize spontaneous mutants of Escherichia coli K-12 exhibiting resistance to PPA, PA, and NAL.
- To investigate the genetic basis of resistance to these quinolone antibiotics.
- To elucidate the differential mechanisms underlying resistance to PPA versus PA and NAL.
Main Methods:
- Isolation of spontaneous mutants from Escherichia coli K-12.
- Phenotypic characterization of drug resistance and susceptibility patterns.
- Genetic mapping of resistance mutations to identify involved genes (nalA, nalC, nalD).
- Analysis of bacterial DNA synthesizing system sensitivity and drug transport mechanisms.
Main Results:
- Mutants displayed varied resistance patterns to PPA, PA, and NAL.
- Some mutants resistant to PA and NAL showed hypersusceptibility to PPA.
- Resistance was conferred by mutations at nalA and novel genes nalC and nalD, located at approximately 82 min on the bacterial map.
- Resistance to PA and NAL involved decreased DNA synthesizing system sensitivity and impaired drug transport.
- Resistance to PPA was solely attributed to decreased DNA synthesizing system sensitivity.
Conclusions:
- Multiple genetic loci (nalA, nalC, nalD) contribute to quinolone resistance in Escherichia coli.
- Differential resistance mechanisms exist for PPA compared to PA and NAL, involving drug transport in addition to target site modification.
- The findings provide insights into the complex interplay between bacterial genetics and antibiotic resistance, informing future drug development and treatment strategies.