Furthermore, our study focussed on only

one plasmid and host (E. coli) combination. Although this combination is relevant, because of its high prevalence in Dutch broilers, other plasmid – host combination might exhibit different behaviour. Plasmid loss was not observed as expected because of the presence of two addiction systems, which account for stable inheritance of the plasmid to daughter cells [22]. The presence of these addiction systems is common in IncI1 plasmids [10]. The reduction of the ESBL-gene carrying plasmid shall thus depend on fitness costs involving reduced growth or maximum density of its host. Conjugation was modelled as a mass Salubrinal mouse action process, which is often used to describe the spread of infectious diseases among host individuals [23]. This mass action assumption is commonly used for modelling the conjugation

process, as it explains mechanistically that at higher concentrations of bacteria, conjugation is more efficient because cells make more frequent contacts [12, 24]. With mass action we assume that the time taken by the actual conjugation process is much smaller than the time between contacts of bacteria, which seems a valid assumption, because much higher conjugation coefficients are found with similar conjugation systems [25]. Furthermore, assuming mass action means that we assume homogeneous mixing, this is thought to occur PRN1371 molecular weight in our in vitro experiments, but might not be the case under natural conditions. When under natural conditions in the gut mixing is not homogeneous, the conjugation will be less efficient because fewer contacts are made. This might lead to a decrease of bacteria carrying the plasmid when small fitness costs exist, which cannot be measured in our in vitro experiments. For our analyses, we used a logistic growth model by Barany and Roberts [18] for which we separated the GSK126 chemical structure population into three subpopulations (D, R and T) and added conjugation and plasmid loss dynamics. The model does not describe a death phase in which the bacterial population dies out. A death phase occurs when the medium in which the populations are grown is depleted of nutrients. Such a death

phase was not observed in the experiments. Therefore, the model was appropriate to describe the MTMR9 population dynamics in our experiments. The conjugation coefficient γ T of the transconjugant was found to be much higher than that of the donor. This might be due to repression of conjugation [9, 26]. By such a mechanism conjugation becomes repressed after a certain period since acquiring the plasmid. Newly formed transconjugants have a transient period in which conjugation is de-repressed and the conjugation coefficient is higher. The population of donors might be in a repressed state such that the increase of transconjugants is slower in the beginning of the experiment, and the accumulation of new transconjugants increases the overall conjugation coefficient.