Fundamental parameters governing the transmission of conjugative plasmids

ABSTRACT Plasmid conjugation is a major route for the dissemination of antibiotic resistances and adaptive genes among bacterial populations. Obtaining precise conjugation rates is thus key to understanding how antibiotic resistances spread. Plasmid conjugation is typically modeled as a density-dependent process, where the formation of new transconjugants is proportional to the rate of encounters between donor and recipient bacteria. By analyzing conjugation dynamics at different cell concentrations, here we show that this assumption only holds at low bacterial densities. At higher concentrations, plasmid transmission switches from a density-dependent process to a frequency-dependent one. Mathematical modeling revealed that plasmid conjugation follows a Hollinǵs Type II functional response, characterized by two fundamental parameters: the searching rate and the handling time. These parameters represent, respectively, the density and frequency dependent limits for plasmid transmission. Our results demonstrate that these parameters are characteristic of the transfer machinery, rather than the entire plasmid genome, and that they are robust to environmental and transcriptional perturbation. Precise parameterization of plasmid conjugation will contribute to a better understanding of the propagation dynamics of antimicrobial resistances.