An interdisciplinary approach to reveal the dynamics of generalized transduction of antimicrobial resistance genes

Antimicrobial resistance (AMR) genes can spread between bacteria by “generalized transduction”, where phages act as vectors to transfer them. However, our knowledge of the dynamics of transduction and how to best represent them is limited. We aimed to fill this gap through an interdisciplinary approach, generating microbiological data and using mathematical models to clarify the underlying transduction dynamics.

We co-cultured two library strains of Methicillin-resistantStaphylococcus aureus, each harbouring a resistance gene for a different antibiotic, with 80α generalized transducing phage. We recorded numbers of bacteria and phages at multiple time-points over 24h, using the presence of bacteria resistant to both antibiotics as evidence that transduction occurred. We developed and compared mathematical models of transduction based on how well they fit to the lab data.

After a growth phase of 8h, bacteria and phage surprisingly coexisted at a stable equilibrium in our culture, the level of which was dependent on the initial concentration of phage. The rate of transducing phage generation was approximately 10-6per lytic phage, sufficient to consistently generate double resistant bacteria, detectable after only 7h. Dynamics of transduction were best captured by a mathematical model in which the rate of phage infection slows as the bacteria population approaches carrying capacity.

The novel data and models generated provide valuable insights into the dynamics of transduction of AMR. This interdisciplinary framework could be extended to other bacterial species, and is the first step towards evaluating the impact of transduction on the overall public health consequences of AMR.