Mutation dynamics in intramacrophage bacteria: How a host-microbe interaction affects antimicrobial resistance

Mutations are fundamental for the evolution of all organisms and adaptation to their environment. They emerge due to replication errors, oxidative stress or various mutagenic stressors. Mutations in bacteria can also drive antimicrobial resistance (AMR), which is a major health problem claiming millions of lives every year. Yet, our understanding on how bacteria adapt and evolve resistance in the human host environment remains unclear.

To develop new approaches to tackle AMR, it is fundamental that we understand how bacteria mutate during colonisation of immune human cells such as macrophages.

We hypothesise that the aggressive environment in the macrophage contributes to the increase of bacterial mutational rate, which drives the adaptation to the host environment and that can, together with antibiotic treatments, lead to AMR.

To test this hypothesis we aim to quantify real-time mutation dynamics in a live bacterium inside a macrophage. Two-dimensional single-molecule-localisation microscopy techniques (2D-SLM) allow real-time monitoring of mutations in a bacterium, already demonstrated for Escherichia coli (E.coli). 2D-SLM localises single proteins that bind a mutation site, reducing the protein's mobility (diffusion coefficient) to near zero. However, 2D-SLM only works on thin samples (