How Conjugation Contributes to Antibiotic Resistance of Biofilm - from an Aspect of Population Balance Model with Stochastic Intracellular Gene Regulation

      In this work, a population balance model with stochastic intracellular gene regulation is applied to analyze the important role of conjugation on biofilm drug resistance. The transfer of conjugative plasmid helps bacteria spread antibiotic resistance. Specifically, we focus on the conjugation of plasmid pCF10, which is influenced by both pheromone, secreted by recipients, and inhibitor, secreted by donors. Mass transfer effects in the biofilm alter the ratio of pheromone to inhibitor of a cell, which  in turn influlences the DNA configuration. Accordingly, the gene expression pattern is altered. Our model predicts that biofilm has a pronounced effect on the induction of conjugation.  Further, the planktonic environment shows unimodal distributions around the on or off states, while the biofilm environment shows bimodal distributions.  While the addition of inhibitor has only a small effect on the biofilm, the effect on cells in planktonic growth is substantial. These results offer a plausible explanation of biofilm antibiotic resistance caused by conjugation.