Persistence of Antibiotic Resistance Plasmids in Biofilms.

摘要

Plasmids play an important role in the spread of genes that confer resistance to antibiotics among bacterial pathogens. Given the worrisome rise of bacterial multi-drug resistance worldwide, the goal of our current research project is to characterize the evolutionary mechanisms by which multi-drug resistance (MDR) plasmids improve their persistence in biofilms formed by important wound pathogens. The central hypothesis of this study is that the evolutionary pathways through which stable plasmid maintenance improves are different and more varied in biofilms than in well-mixed liquid cultures due to the uniquely spatially structured environment of biofilms. To address this hypotheses the following aims are being addressed: (i) Compare the persistence of MDR plasmids in populations of clinically relevant bacteria grown in biofilms and well-mixed liquid cultures; (ii) Compare the evolution of plasmid persistence in bacteria grown in biofilms and well-mixed liquids; (iii) Characterize evolutionary changes that occur during stabilization of plasmid-host pairs under both conditions. During the first year of this two-year study, we accomplished several aspects of the first two tasks outlined in the SOW. Our preliminary results indicate that the structured biofilm environment, which typically characterizes the type of bacterial growth in wounds, facilitates the persistence of MDR plasmids in Acinetobacter baumannii, a problematic wound pathogen. Moreover, we have shown that plasmids coevolved with their host under antibiotic selection for 50 days have improved their persistence in part by undergoing large structural changes. While still partially uncharacterized, these genetic modifications likely decrease plasmid cost to the host while retaining favorable plasmid-encoded traits (i.e. antibiotic resistance).