AMR Evolution, Conjugative Plasmids, Phage Therapy, and CRISPR Antimicrobials

Dr. Ilmur Jonsdottir, postdoctoral researcher at the University of Jyväskylä, will present her PhD research:

From Finland (with a Sword): My Doctoral Research on AMR Evolution, Conjugative Plasmids, Phage Therapy, and CRISPR Antimicrobials

Antimicrobial resistance (AMR) has emerged as a pressing global crisis that threatens to undermine a century of medical advancements and poses significant implications to healthcare worldwide. 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. This thesis delves into the antimicrobial resistance and plasmid dynamics of Enterobacteriaceae members E. coli and K. pneumoniae. The overarching aim of this thesis is to explore various aspects of microbial dynamics and antibiotic resistance evolution. Firstly, the investigation aims to delve into the dynamics of plasmids and resistance following antibiotic therapy (Study I). Secondly, it examines the evolutionary dynamics of plasmid lineages and their potential for evolutionary rescue (Study II). Furthermore, it aims to explore the environmental determinants influencing the development of phage resistance (Study III). Lastly, it aims to investigate the evolution and persistence of an ESBL plasmid targeted by CRISPR antimicrobial strategies (Study IV). Findings reveal significant AMR and plasmid content diversity among multiresistant E. coli and K. pneumoniae gut isolates. Notably, the research underscores the critical role of ecological factors in shaping the efficacy of interventions like phage therapy and CRISPR antimicrobials. Moreover, it highlights the profound influence of evolutionary history on plasmid dynamics and resistance mechanisms. This thesis expands current knowledge by shedding light on the adaptability of bacteria to their environment and emphasizes the need to consider ecological factors in developing effective strategies against the AMR crisis.