Variation in Mutant Prevention Concentrations.

Area of Science:

• Evolutionary biology
• Microbiology
• Genetics

Background:

• Understanding phenotypic trait variation is crucial for evolutionary biology.
• Antibiotic resistance in bacteria is often characterized by minimum inhibitory concentration (MIC), which typically shows low strain-specific variation.
• The mutant prevention concentration (MPC), representing the MIC of the most resistant sub-population, is less understood regarding its variability.

Purpose of the Study:

• To investigate the variability of the mutant prevention concentration (MPC) within a single bacterial strain-antibiotic combination.
• To determine how MPC distributions change with the evolution of antibiotic resistance.

Main Methods:

• Used a Staphylococcus species and five distinct antibiotic classes (ciprofloxacin, doxycycline, gentamicin, nitrofurantoin, oxacillin).
• Examined resistance frequencies across a wide range of antibiotic concentrations.
• Measured the repeatability of the MPC, defined as the minimum antibiotic concentration preventing survival in a 10^10 bacterial population.

Main Results:

• Observed substantial variation in MPC values for a given strain-antibiotic pair.
• Found that MPC distributions were typically non-normal.
• Demonstrated that evolved antibiotic resistance led to wider and sometimes multi-modal MPC distributions.

Conclusions:

• Contrary to the MIC, the MPC exhibits high variability for specific bacterial strain-antibiotic combinations.
• The variability of MPC is influenced by the evolution of antibiotic resistance.