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Résilience aux antibiotiques de biofilms bactériens : concepts, modélisation et expérimentation

Abstract : Bacterial systems are complex and adaptive. When faced with disturbances, such as antibiotic treatments, they survive, recover and evolve. This is particularly true for biofilms, which survive treatments that planktonic cells cannot overcome. The capacity of systems to recover their initial state, some of their functions or composition after a disturbance is called resilience. The resilience concept is often considered complementary to resistance in ecology. However, antibiotic resilience has received little attention compared to antibiotic resistance. One reason of this lack of interest comes from the fact that the resilience concept is often poorly defined and ambiguous. In this thesis, we firstly developed a conceptual framework of antibiotic resilience and applied this framework to the case of a bacterial population faced with antibiotics. This analysis highlighted the importance of the biological mechanism of bacterial persistence. This phenomenon is based on the formation of sub-populations of antibiotic tolerant cells, the persisters, which is influenced by environmental conditions. To relate persister formation to environmental conditions, we developed mathematical models of phenotypic switches between susceptible and persister cells and calibrated and tested them with experimental data. Lastly, we studied the influence of bacterial persistence on biofilm antibiotic resilience. For this purpose, we developed an individual-based model of biofilm with phenotypic switches between susceptible and persister cells. Different strategies of phenotypic switches were related to the dynamics of growth, survival and recovery of bacterial biofilms faced with antibiotic shocks. The setting up of experimentations to obtain data to compare to simulations is presented in the discussion of this thesis. Globally, this thesis contributes to the clarification of the concept of antibiotic resilience and to the understanding of bacterial persistence in biofilms. It gives new perspectives on the use of the resilience concept in clinical bacteriology and emphasizes the importance of the heterogeneity of bacterial populations in their capacity to face disturbances and evolve.
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  • HAL Id : tel-01787183, version 1
  • IRSTEA : PUB00057150

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Gabriel Carvalho. Résilience aux antibiotiques de biofilms bactériens : concepts, modélisation et expérimentation. Bio-informatique [q-bio.QM]. Université Clermont Auvergne, 2017. Français. ⟨NNT : 2017CLFAC068⟩. ⟨tel-01787183⟩

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