"The efficiency of resensitizing CRISPR-encoding plasmids for the treatment of AMR bacteria"Kippnich, JohannesThe spread of antibiotic resistance among pathogens poses a significant threat to human health. In particular, plasmids, small circular DNA molecules found in bacteria, often harbor genes encoding antibiotic resistance traits. This facilitates the spread and emergence of multiresistant strains, outpacing the development of new antibiotics. The sequence specificity of the revolutionary CRISPR-Cas system offers a promising alternative approach to combating antibiotic resistance. By introducing CRISPR-encoding plasmids that specifically target antibiotic resistance genes on resistance plasmids, the susceptibility of bacteria to antibiotics can be restored. However, genetic variations within bacterial populations can hinder the effectiveness of the CRISPR-Cas system. In this study, we model the efficiency of resensitization of bacterial populations via CRISPR, followed by antibiotic treatment. We assess the treatment success rate depending on plasmid copy numbers, compatibility between the CRISPR plasmid and the resistance conferring plasmid, and the dominance relationship between mutant and wild-type plasmids. Our results identify promising approaches to combat antibiotic resistance with CRISPR-encoding plasmids: For low plasmid copy numbers, cleaving by CRISPR systems on incompatible plasmids is most effective, while for higher copy numbers, silencing by CRISPR systems on compatible plasmids offer the optimal solution. |
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