Evolution and spread of multidrug resistant pathogens in a spatially heterogeneous environment

Abstract

The emergence and the spread of multi-adapted pathogens is often viewed as a slow process resulting from the incremental accumulation of single adaptations. In bacteria, for instance, multidrug resistance to antibiotics may result from the sequential acquisition of single drug resistance to different antibiotics. In phytopathogens, the ability to infect different resistant varieties of crops may also result from the accumulation of distinct virulence genes. Here we use a general epidemiological model to analyse the evolution of pathogen adaptations throughout an epidemic spreading in a heterogeneous host population where selection varies periodically in space. This spatially heterogeneous selection may result from the use of different drugs, different vaccines or different crop varieties in agriculture. We study both the transient evolution of pathogen adaptation at the front of the epidemic and the long-term evolution far behind the epidemic front. We identify five different types of epidemic profiles that may arise from different combinations of spatial heterogeneity and the cost of multi-adaptation. In particular, we show that multi-adaptation can drive epidemic spread, while the evolution of single-adaptation may only occur in a second phase, when the pathogen specializes on local selective pressures. Indeed, a generalist pathogen with multiple adaptations can outpace the spread of a coalition of specialist pathogens when selection varies frequently in space. This result is amplified in finite host populations because demographic stochasticty can lead to the extinction of maladapted pathogens specialised to a local selective pressure. Our work has important implications for the management of multiple drugs and vaccines against pathogens but also for the optimal deployment of resistant varieties in agriculture.