Examining recombination and intra-genomic conflict dynamics in the evolution of anti-microbial resistant bacteria

The spread of antimicrobial resistance (AMR) among pathogenic bacterial species threatens to undercut much of the progress made in treating infectious diseases. AMR genes can disseminate between and within populations via horizontal gene transfer (HGT). Selfish mobile genetic elements (MGEs) can encode resistance and spread between host cells. Homologous recombination can alter the core genes of pathogens with resistant donors via HGT too. MGEs may be cured from host genomes through transformation. Hence, MGEs may be able to avoid deletion by disrupting transformation. This work aims to understand how the dynamics of these processes affect the epidemiology of AMR pathogens. To understand these dynamics, I co-developed a new version of the popular recombination detection tool Gubbins. Through simulation studies, I find this new version to be both accurate in reconstructing the relationships between isolates, and efficient in terms of its use of computational resources. I then apply Gubbins to both AMR lineages and species-wide datasets of the pathogen Streptococcus pneumoniae. I find that recombination frequently occurs around core genes involved in both drug resistance and the host immune response. Additionally, an MGE was able to successfully spread within a population by disrupting the transformation machinery, preventing its loss from the host. Finally, I investigate two recent examples of MGEs disrupting transformation in the gram-negative species Acinetobacter baumannii and Legionella pneumophila. I find that while these insertions may decrease the efficiency of transformations within cells, the observed recombination rates largely reflect the selection pressures on isolates. With MGEs only partially able to inhibit these observable transformation events. These results show how selection pressures from clinical interventions shape pathogen genomes through diverse, often interspecies, recombination events. The spread of MGEs can also be favoured by both these selection pressures, and their ability to disrupt host cell machinery.Open Acces

The HBP1 tumor suppressor is a negative epigenetic regulator of MYCN driven neuroblastoma through interaction with the PRC2 complex

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