Doctoral researcher Ilmur Jonsdottir presents her dissertation research: "Evolutionary Trajectories of Conjugative Resistance Plasmids and Their Interplay in the Ecology of Clinically Relevant Bacteria".
ABSTRACT: Antimicrobial resistance (AMR) has emerged as a pressing global crisis that threatens to undermine a century of medical advancements and poses significant implications to treat bacterial infections in healthcare. The complexity of AMR, particularly evident in notorious pathogens like those within the Enterobacteriaceae family, is exacerbated by the horizontal dissemination of antimicrobial resistance encoding genes (ARGs). This propagation within bacterial communities is further accelerated by self-replicating and self-transferrable mobile genetic elements (MGEs), known as conjugative plasmids. Therefore, novel ways to combat AMR and its dispersal are needed. In phage therapy, bacteria-infecting phages are harnessed against pathogenic bacteria. Further, antimicrobial CRISPR-tools may be a future solution to diminish ARGs from microbial communities. The overarching aim of this thesis was to explore various aspects of plasmid dynamics and antibiotic resistance evolution in Enterobacteriaceae members Escherichia coli and Klebsiella pneumoniae. Firstly, the investigation aimed to delve into the dynamics of plasmids and resistance following antibiotic therapy (Study I). Secondly, it examined the evolutionary dynamics of plasmid lineages and their potential for evolutionary rescue via conjugative plasmids (Study II). Furthermore, it aimed to explore the environmental determinants influencing the development of phage resistance (Study III). Lastly, it aimed to investigate the evolution and persistence of an Extended-Spectrum Beta-lactamase (ESBL)-plasmid targeted by CRISPR antimicrobial strategies (Study IV). The research clearly demonstrates that the effectiveness of targeted solutions utilizing phages or CRISPR-antimicrobials against pathogenic bacteria is impeded by the development of bacterial resistance, emphasizing the pivotal role of ecological factors in shaping these interventions. Furthermore, the findings highlight the significant challenge posed by the adaptability of AMR-disseminating plasmids to various host environments, revealing the profound influence of evolutionary history on plasmid dynamics. This thesis expands current knowledge by shedding light on the responsiveness of bacteria to their environment and emphasizes the need to consider ecological factors in developing effective strategies against the AMR crisis.
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