Contributors: Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS); Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516 (LASIRE); Institut de Chimie - CNRS Chimie (INC-CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS); This work was supported by the French National Centre for Scientific Research (CNRS), the National Institute for Health and Medical Research (INSERM), the Institute Pasteur of Lille, the University of Lille, the European Regional Development Fund as part of the Action de recherche concertée d’initiative régionale program (grant 10090077-Présage 35712 to F.S.), grants of the Agence National de la Recherche (07-MIME-017-01 IVOTIMP to F.S. and ANR-21-CE15-0047 to S.B.G.), and a grant of the Investments for the Future program managed by the Agence National de la Recherche (ANR-16-IDEX-0004 ULNE to S.B.G.). ICP-AES and ICP-MS measurements were performed on the Chevreul Institute Platform (U-Lille/CNRS). The Region Hauts de France and the French government are warmly acknowledged for the co-funding of these apparatus. The funding bodies were not involved in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript.; ANR-21-CE15-0047,RESISTANT,Rôle d'un système de signalisation cellulaire dans l'adaptation de Yersinia pestis à son vecteur(2021); ANR-16-IDEX-0004,ULNE,ULNE(2016)
نبذة مختصرة : International audience ; The adaptation of Yersinia pestis , the flea-borne plague agent, to fluctuating environmental conditions is essential for the successful colonization of the flea vector. A previous comparative transcriptomic analysis showed that the Cpx pathway of Y. pestis is up-regulated in infected fleas. The CpxAR two-component system is a component of the envelope stress response and is critical for maintaining the integrity of the cell. Here, a phenotypic screening revealed a survival defect of the cpxAR mutant to oxidative stress and copper. The measured copper concentration in the digestive tract contents of fed fleas increased fourfold during the digestive process. By direct analysis of phosphorylation of CpxR by a Phos-Tag gel approach, we demonstrated that biologically relevant concentrations of copper triggered the system. Then, a competitive challenge highlighted the role of the CpxAR system in bacterial fitness during flea infection. Lastly, an in vitro sequential exposure to copper and then H 2 O 2 to mimic the flea suggests a model in which, within the insect digestive tract, the CpxAR system would be triggered by copper, establishing an oxidative stress response. IMPORTANCE The bacterium Yersinia pestis is the agent of flea-borne plague. Our knowledge of the mechanisms used by the plague bacillus to infect the flea vector is limited. The up-regulation of the envelope stress response under the control of the Cpx signaling pathway was previously shown in a transcriptomic study. Here, our in vivo and in vitro approaches suggest a model in which Y. pestis uses the CpxAR phosphorelay system to sense and respond to the copper present in the flea gut, thereby optimizing the flea gut colonization. In other words, the system is essential for bacterial fitness in the flea.
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