Plasmid stability in fluctuating environments: population genetics of multi-copy plasmids

Abstract

Plasmids are extra-chromosomal genetic elements that encode a wide variety of phenotypes and can be maintained in bacterial populations through vertical and horizontal transmission, thus increasing bacterial adaptation to hostile environmental conditions like those imposed by antimicrobial substances. To circumvent the segregational instability resulting from randomly distributing plasmids between daughter cells upon division, non-transmissible plasmids tend to be carried in multiple copies per cell, which also results in a metabolic burden to the bacterial host, therefore reducing the overall fitness. This trade-off poses an existential question for plasmids: What is the optimal plasmid copy number? We address this question using a combination of population genetics modeling with microbiology experiments consisting of Escherichia coli K12 bearing a multi-copy plasmid encoding for blaTEM-1, a gene conferring resistance to b-lactam antibiotics. We use a Wright-Fisher model to evaluate the interaction between the above mentioned opposing forces. By numerically determining the optimal plasmid copy number for constant and fluctuating selection regimes, we conclude that plasmid copy number is an optimized evolutionary trait that depends on the rate of environmental fluctuation and balances the benefit between increased stability in the absence of selection with the burden associated with carrying multiple copies of the plasmid.