Speaker
Description
Cecilia Fruet, Ella Müller, Claude Loverdo, Anne-Florence Bitbol
A population composed only of drug-sensitive bacteria cannot survive the addition of a biostatic drug at a sufficiently high concentration and for sufficiently long. However, if at least one resistant bacterium is present before drug addition, it can lead to population rescue through resistance. How does spatial structure impact the survival of a bacterial population upon biostatic drug addition? We considered a minimal individual based model, starting with only sensitive bacteria, and focused on de novo appearance of resistance, with resistant mutants arising from mutations upon division. When including a substantial fitness cost of resistance, we did not observe any impact of structure in our minimal model. Therefore, we focused on neutral resistance mutations. This case is relevant because resistance mutations are often effectively neutral, e.g. at low drug concentrations. As a minimal model of spatial structure, we considered a clique structure with per-capita migration rate γ. This structure becomes a well-mixed population for large γ, and a fully structured population with isolated demes if γ is zero.
We found that the probability that the population survives upon biostatic drug application after a variable amount of time is affected by population structure. This is due to the different system composition for the different population structures at a given time. Although the survival probability is maximum in the structured population at all times, once the drug is applied, the demes that have no preexisting resistant mutants will go extinct. Conversely, as soon as one allows bacteria to migrate, mutants can spread in the whole system. We calculated analytically the time to colonize the next deme due to migrations, allowing us to compare timescales in the process. Overall, we found that in a minimal model, spatial structure can favor the survival of a bacterial population by de novo resistance upon application of a biostatic drug. Our main conclusions also extend to biostatic drugs and to other structures (lattice, star).
