Sub-inhibitory antibiotic treatment selects for enhanced metabolic efficiency

Area of Science:

• Microbiology
• Evolutionary Biology
• Biochemistry

Background:

• Bacterial growth and metabolism are linked, but antibiotic selection creates a paradox favoring fast growth and slow metabolism.
• Antibiotic resistance is typically studied in terms of growth, with less known about metabolic changes.

Purpose of the Study:

• To investigate how antibiotic selection impacts bacterial metabolic efficiency.
• To determine if enhanced metabolic efficiency is a selectable trait during antibiotic treatment.
• To explore if metabolic efficiency can be targeted for re-sensitization strategies.

Main Methods:

• Mathematical modeling of bacterial populations under sub-inhibitory antibiotic selection.
• Adaptive laboratory evolution experiments using *Escherichia coli* and carbenicillin.

Main Results:

• Simulations predicted that sub-inhibitory antibiotic concentrations select for enhanced metabolic efficiency (better nutrient utilization).
• Drug-adapted bacteria achieved similar biomass with less substrate, independent of growth rate.
• Restoring metabolic efficiency re-sensitized resistant bacteria to antibiotics in experimental evolution.

Conclusions:

• Metabolic efficiency is under direct selective pressure during antibiotic treatment.
• Evolutionary context influences antibiotic efficacy and re-sensitization strategies.
• Targeting metabolic efficiency offers a potential approach to combat antibiotic resistance.