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Mécanismes d’acquisition du fer chez Bacillus cereus : rôles d’IlsA, du système Isd et des sidérophores dans l’assimilation du fer à partir de l’hème et de la ferritine

Abstract : In host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the limited iron bioavailability in the host, bacteria have developed several strategies to acquire iron during infection. In the human opportunistic bacteria Bacillus cereus, a particular NEAT-LRR domain protein named IlsA (Iron-regulated leucine rich surface protein) was previously identified as a surface protein involved in iron acquisition from both hemoproteins and ferritin. In this study, we characterized the function of IlsA and the IlsA-NEAT domain and their involvement in heme and hemoglobin binding. Our results show that IlsA binds heme via the NEAT domain with a 1:1 stoichiometry and that this domain is able to extract heme from hemoglobin. Furthermore, the dynamic interplay between IlsA and the B.cereus Isd system (Iron surface determinant) involved in heme acquisition in other Gram-positive bacteria has been investigated. Following direct protein-protein interaction, we observe a heme transfer from holo-IlsA to apo-IsdC.The molecular basis of iron assimilation from host-ferritin by pathogens remains largely unknown. Here, we show that IlsA interacts directly with several forms of ferritins, causing ferritin aggregation on the bacterial surface, leading to an increase in iron release from the ferritin nanocages. In addition, the binding stoichiometry of 24 IlsA for 1 ferritin evidence an interaction between IlsA and each subunit of the ferritin shell. Finally, a B. cereus strain disrupted in bacillibactin production was markedly affected both in ferritin acquisition and in virulence in an insect model, suggesting a possible partnership between siderophores and IlsA in iron uptake from ferritin. Globally, this study highlights the interplay between surface proteins and siderophores and provides new insight into host adaptation of B. cereus.Key words: Iron, Bacillus cereus, IlsA, NEAT, IsdC, heme, hemoglobin, ferritins, siderophore.
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  • HAL Id : tel-03580649, version 1

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Elise Abi Khalil. Mécanismes d’acquisition du fer chez Bacillus cereus : rôles d’IlsA, du système Isd et des sidérophores dans l’assimilation du fer à partir de l’hème et de la ferritine. Microbiologie et Parasitologie. AgroParisTech; Université Saint-Joseph (Beyrouth). Faculté des Sciences, 2013. Français. ⟨NNT : 2013AGPT0039⟩. ⟨tel-03580649⟩

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