Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal.
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal.
Curr Biol. 2022 Aug 8;32(15):3261-3275.e4. doi: 10.1016/j.cub.2022.06.017. Epub 2022 Jul 5.
Iron is critical in host-microbe interactions, and its availability is tightly regulated in the mammalian gut. Antibiotics and inflammation can perturb iron availability in the gut, which could alter host-microbe interactions. Here, we show that an adaptive allele of iscR, a major regulator of iron homeostasis of Escherichia coli, is under fluctuating selection in the mouse gut. In vivo competitions in immune-competent, immune-compromised, and germ-free mice reveal that the selective pressure on an iscR mutant E. coli is modulated by the presence of antibiotics, the microbiota, and the immune system. In vitro assays show that iron availability is an important mediator of the iscR allele fitness benefits or costs. We identify Lipocalin-2, a host's immune protein that prevents bacterial iron acquisition, as a major host mechanism underlying fluctuating selection of iscR. Our results provide a remarkable example of strong fluctuating selection acting on bacterial iron regulation in the mammalian gut.
铁在宿主-微生物相互作用中至关重要，其在哺乳动物肠道中的可用性受到严格调控。抗生素和炎症会扰乱肠道中的铁供应，从而改变宿主-微生物相互作用。在这里，我们表明大肠杆菌铁稳态主要调节因子 iscR 的适应性等位基因在小鼠肠道中受到波动选择。在免疫功能正常、免疫功能受损和无菌小鼠中的体内竞争表明，抗生素、微生物群和免疫系统的存在会调节 iscR 突变大肠杆菌的选择压力。体外实验表明，铁供应是 iscR 等位基因适应度收益或成本的重要介导物。我们确定了脂联素-2（一种阻止细菌铁摄取的宿主免疫蛋白）作为 iscR 波动选择的主要宿主机制。我们的研究结果提供了一个极好的例子，即在哺乳动物肠道中，强烈的波动选择作用于细菌的铁调节。
