Clonal Interference and Mutation Bias in Small Bacterial Populations in Droplets

Area of Science:

• Evolutionary biology
• Microbiology
• Genetics

Background:

• Experimental evolution often uses large populations, not reflecting microbial pathogens' small population dynamics.
• Understanding adaptation in small populations is crucial for pathogen evolution and treatment.

Purpose of the Study:

• To investigate adaptation mechanisms in small populations of *Escherichia coli* under antibiotic stress.
• To compare the adaptive potential of wild-type and high-mutation-rate strains in limited population sizes.

Main Methods:

• Evolving wild-type and mutator *Escherichia coli* strains for ~100 generations in small-volume millifluidic droplets.
• Assessing adaptation to the β-lactam antibiotic cefotaxime with an effective population size of ~27,000 cells.

Main Results:

• Small population size restricted wild-type adaptation to modest fitness gains via outer-membrane vesicle production.
• Mutator strains, with ~30x higher mutation rates, adapted faster through porin inactivation and efflux pump upregulation/activation.
• Clonal interference and mutation bias influenced adaptive pathways in small populations.

Conclusions:

• Limited population size and mutation rate significantly impact bacterial adaptive trajectories.
• High mutation rates can overcome limitations in small populations, enabling faster adaptation via specific genetic mechanisms like efflux pump modulation.
• Findings highlight the interplay of mutation bias and population size in microbial evolution and antibiotic resistance.