Ariel B. Lindner, Sabine Rakotobe, François Taddei, Marianne De Paepe, Antoine Giraud, Jean-Christophe Bambou, Valérie Gaboriau-Routhiau, Safia Arous, Nadine Cerf-Bensussan, Génétique moléculaire, évolutive et médicale, IFR65-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA), Department of Medical Biochemistry and Microbiology, Uppsala University, Université Paris Descartes - Paris 5 (UPD5), U793, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche d'Écologie et Physiologie du Système Digestif (UEPSD), Giraud, Antoine, Arous, Safia, De Paepe, Marianne, Gaboriau Routhiau, Valérie, Lindner, Ariel B., Taddei, François, Cerf-Bensussan, Nadine, and ProdInra, Migration
While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in EnvZ/OmpR two-component signal transduction system, which controls more than 100 genes. The selective advantage conferred by the mutations that modulate EnvZ/OmpR activities was the result of their independent and additive effects on flagellin expression and permeability. These results obtained in vivo thus suggest that global regulators may have evolved to coordinate activities that need to be fine-tuned simultaneously during adaptation to complex environments and that mutations in such regulators permit adjustment of the boundaries of physiological adaptation when switching between two very distinct environments., Author Summary The mammalian intestine is a privileged physiological site to study how coevolution between hosts and the trillions of bacteria present in the microbiota has shaped the genome of each partner and promoted the development of mutualistic interactions. Herein we have used germ-free mice, a simplified albeit ecologically relevant system, to analyse intestinal adaptation of a model bacterial strain, Escherichia coli MG1655. Our results show that single point mutations in the ompB master regulator confer a striking selective adaptive advantage. OmpB comprises EnvZ, a transmembrane sensor with a dual kinase/phosphatase activity, and OmpR, a transcription factor controlling more than 100 target genes. In response to environmental changes, EnvZ modulates the phosphorylation and thereby the transcriptional activity of OmpR. We further show that the selective advantage conferred by OmpB mutations is related to their additive and independent effects on genes regulating permeability and flagellin expression, two major set of genes controlled by OmpR. These results suggest that global regulators may have evolved to coordinate physiological activities necessary for adaptation to complex environments and that mutations offer a complementary genetic mechanism to adjust the scale of the physiological regulation controlled by these regulators in distinct environments.