Multidrug-resistant bacteria compensate for the epistasis between resistances

Area of Science:

• Microbiology
• Evolutionary Biology
• Genetics

Background:

• Antibiotic resistance mutations often impose a fitness cost on bacteria.
• Compensatory mutations can mitigate these costs, aiding resistance maintenance.
• Compensation mechanisms for multiple resistances are poorly understood, especially considering epistatic interactions.

Purpose of the Study:

• To investigate the compensatory evolution of bacteria with dual antibiotic resistance (streptomycin and rifampicin).
• To compare the compensatory process in double-resistant bacteria with that of single-resistant strains.
• To elucidate the role of epistasis in compensatory evolution of antibiotic resistance.

Main Methods:

• Experimental evolution of Escherichia coli strains.
• Next-generation sequencing for genomic analysis.
• In silico simulations and genome editing.
• Fitness assays in different genetic backgrounds.

Main Results:

• Double-resistant bacteria exhibit faster compensation than single-resistant strains.
• Compensatory mutations in double-resistant strains have larger fitness effects.
• Novel mutations were identified that specifically compensate for double resistance, being neutral or detrimental in other backgrounds.
• These compensatory mutations counteract epistasis between resistance alleles.

Conclusions:

• Epistasis between antibiotic resistances can drive rapid compensatory evolution.
• Compensatory mutations can stabilize costly multiple resistances by overcoming epistatic interactions.
• Understanding these mechanisms is crucial for predicting the spread of antibiotic resistance.