Positive R plasmid mutator effect on chromosomal mutation to nalidixic acid resistance in nalidixic acid-exposed...

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• Mutator plasmids can increase spontaneous mutation rates in bacteria.
• Quinolone resistance is a significant clinical concern.
• Understanding the genetic basis of bacterial resistance is crucial for public health.

Purpose of the Study:

• To investigate the effect of specific mutator plasmids (R46, R391, pYD1) on nalidixic acid resistance mutation frequencies in Escherichia coli.
• To determine if the non-mutator plasmid RP4 affects mutation rates.
• To assess how sub-lethal concentrations of nalidixic acid impact apparent mutation frequencies.

Main Methods:

• Determining mutation frequencies to nalidixic acid resistance in Escherichia coli AB1157 derivatives carrying different plasmids.
• Culturing strains in drug-free broth and in the presence of nalidixic acid.
• Analyzing mutation frequencies under exponential growth and after exposure to sub-lethal drug concentrations.

Main Results:

• Mutator plasmids R46, R391, and pYD1 increased spontaneous mutation frequencies to nalidixic acid resistance.
• Plasmid RP4 did not affect mutation frequencies.
• Exposure to nalidixic acid significantly enhanced apparent mutation frequencies, particularly in strains with mutator plasmids, reaching up to 447-fold higher than controls.

Conclusions:

• Mutator plasmids, even those with modest increases in spontaneous mutation, can contribute to the development of clinically significant quinolone resistance.
• Bacterial adaptation under antibiotic pressure can rapidly increase resistance levels.
• These findings highlight the role of mutator elements in bacterial evolution and antibiotic resistance.