Fluctuating selection on bacterial iron regulation in the mammalian gut

Iron is critical in host-microbe interactions, and its availability is tightly regulated in the mammalian gut. An-tibiotics 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 un-der fluctuating selection in the mouse gut. In vivo competitions in immune-competent, immune -compro-mised, 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 regu-lation in the mammalian gut.

Automated summary

Iron availability is tightly regulated in the mammalian gut, and the adaptive allele of the iron regulation gene iscR undergoes fluctuating selection influenced by antibiotics, microbiota, and the immune system. Host immune protein Lipocalin-2 plays a major role in shaping the selection on iscR.