Within-host dynamics shape antibiotic resistance in commensal bacteria

Area of Science:

• Microbiology
• Epidemiology
• Evolutionary Biology

Background:

• Antibiotic resistance poses a significant global health threat.
• Current models of bacterial transmission fail to explain the stable coexistence of resistant and non-resistant strains observed in populations.
• Understanding the drivers of this coexistence is crucial for effective resistance management.

Purpose of the Study:

• To investigate the role of within-host competition in the coexistence of antibiotic-resistant and sensitive bacterial strains.
• To develop a model that accurately reflects empirical observations of resistance patterns.

Main Methods:

• Embedding mechanistically explicit within-host pathogen dynamics into a structurally neutral transmission model.
• Analyzing the impact of within-host competition on pathogen evolution and population-level dynamics.

Main Results:

• The model successfully reproduced observed patterns of antibiotic resistance for *Escherichia coli* and *Streptococcus pneumoniae* across European countries.
• Within-host competition was identified as a key factor promoting the coexistence of resistant and sensitive strains.
• The model highlights how within-host dynamics modulate the intensity and outcomes of competition, influencing resistance evolution.

Conclusions:

• Competition between resistant and sensitive strains within individual hosts confers a relative fitness advantage to rare resistant strains.
• This within-host competition mechanism explains the stable coexistence of bacterial strains across various antibiotic consumption rates.
• The findings provide a new framework for understanding and managing the spread of antibiotic resistance.